PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32760266-5 2020 Iron has been shown to promote aggregation and pathogenicity of the characteristic aberrant proteins, beta-amyloid, tau, alpha-synuclein, and TDP43, in these diseases. Iron 0-4 synuclein alpha Homo sapiens 121-136 33440237-6 2021 In addition, special attention is addressed to the possible relationship between cellular iron overload and key pathological features of selected neurodegenerative diseases, such as beta-amyloid and tau proteins, alpha-synuclein, and demyelination. Iron 90-94 synuclein alpha Homo sapiens 213-228 33441545-4 2021 We detected that iron deposition was clearly increased in a time-dependent manner from 1 to 17 months in the substantia nigra and globus pallidus, highly contrasting to other brain regions after treatments with alpha-syn PFFs. Iron 17-21 synuclein alpha Homo sapiens 211-220 33441545-7 2021 The brain region-enriched and cell-type-dependent iron localizations indicate that the intranasal alpha-syn PFFs treatment-induced iron depositions in microglia in the substantia nigra may appear as an early cellular response that may initiate neuroinflammation in the dopaminergic system before cell death occurs. Iron 50-54 synuclein alpha Homo sapiens 98-107 33441545-7 2021 The brain region-enriched and cell-type-dependent iron localizations indicate that the intranasal alpha-syn PFFs treatment-induced iron depositions in microglia in the substantia nigra may appear as an early cellular response that may initiate neuroinflammation in the dopaminergic system before cell death occurs. Iron 131-135 synuclein alpha Homo sapiens 98-107 32726602-6 2021 Interestingly, alpha-syn has been functionally linked with the metabolism of both iron and lipid, suggesting a possible interplay between dysregulated alpha-syn and other PD pathological hallmarks related to ferroptosis. Iron 82-86 synuclein alpha Homo sapiens 15-24 32726602-6 2021 Interestingly, alpha-syn has been functionally linked with the metabolism of both iron and lipid, suggesting a possible interplay between dysregulated alpha-syn and other PD pathological hallmarks related to ferroptosis. Iron 82-86 synuclein alpha Homo sapiens 151-160 32629061-0 2020 Copper and iron ions accelerate the prion-like propagation of alpha-synuclein: A vicious cycle in Parkinson"s disease. Iron 11-15 synuclein alpha Homo sapiens 62-77 32629061-4 2020 Here, we reported that copper/iron ions accelerate prion-like propagation of alpha-synuclein fibrils by promoting cellular internalization of alpha-synuclein fibrils, intracellular alpha-synuclein aggregation and the subsequent release of mature fibrils to the extracellular space to induce further propagation. Iron 30-34 synuclein alpha Homo sapiens 77-92 32629061-4 2020 Here, we reported that copper/iron ions accelerate prion-like propagation of alpha-synuclein fibrils by promoting cellular internalization of alpha-synuclein fibrils, intracellular alpha-synuclein aggregation and the subsequent release of mature fibrils to the extracellular space to induce further propagation. Iron 30-34 synuclein alpha Homo sapiens 142-157 32629061-4 2020 Here, we reported that copper/iron ions accelerate prion-like propagation of alpha-synuclein fibrils by promoting cellular internalization of alpha-synuclein fibrils, intracellular alpha-synuclein aggregation and the subsequent release of mature fibrils to the extracellular space to induce further propagation. Iron 30-34 synuclein alpha Homo sapiens 142-157 32629061-5 2020 Mechanistically, copper/iron ions enhanced alpha-synuclein fibrils internalization was mediated by negatively charged membrane heparan sulfate proteoglycans (HSPGs). Iron 24-28 synuclein alpha Homo sapiens 43-58 32629061-6 2020 alpha-Synuclein fibrils formed in the presence of copper/iron ions were more cytotoxic, causing increased ROS production, cell apoptosis, and shortened the lifespan of a C. elegans PD model overexpressing human alpha-synuclein. Iron 57-61 synuclein alpha Homo sapiens 0-15 32629061-6 2020 alpha-Synuclein fibrils formed in the presence of copper/iron ions were more cytotoxic, causing increased ROS production, cell apoptosis, and shortened the lifespan of a C. elegans PD model overexpressing human alpha-synuclein. Iron 57-61 synuclein alpha Homo sapiens 211-226 32629061-8 2020 Together, our results suggest a new role for heavy metal ions, e.g. copper and iron, in the pathogenesis of PD through accelerating prion-like propagation of alpha-synuclein fibrils. Iron 79-83 synuclein alpha Homo sapiens 158-173 33177988-3 2020 Here, we hypothesized that hepcidin could further decrease alpha-syn accumulation via reducing iron. Iron 95-99 synuclein alpha Homo sapiens 59-68 32341450-0 2020 Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation. Iron 64-68 synuclein alpha Homo sapiens 0-15 32409771-0 2020 Correction: Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation. Iron 76-80 synuclein alpha Homo sapiens 12-27 32574378-0 2020 H63D variant of the homeostatic iron regulator (HFE) gene alters alpha-synuclein expression, aggregation, and toxicity. Iron 32-36 synuclein alpha Homo sapiens 65-80 32574378-2 2020 Previous studies have suggested that iron accumulation contributes to the Parkinson"s disease pathology through reactive oxygen species production and accelerated alpha-synuclein aggregation. Iron 37-41 synuclein alpha Homo sapiens 163-178 32574378-3 2020 This study examines the effects of commonly occurring H63D variant of the homeostatic iron regulatory (HFE) gene on alpha-synuclein pathology in cell culture and animal models. Iron 86-90 synuclein alpha Homo sapiens 116-131 32623334-2 2020 We hypothesize that abnormal iron accumulation is a common thread underlying the emergence of the hallmarks of PD, namely mitochondrial dysfunction and alpha-synuclein accumulation. Iron 29-33 synuclein alpha Homo sapiens 152-167 32623334-6 2020 In addition, hepcidin decreased alpha-synuclein accumulation and promoted clearance of alpha-synuclein through decreasing iron content that leads to activation of autophagy. Iron 122-126 synuclein alpha Homo sapiens 87-102 33041329-0 2021 Correction: Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation. Iron 76-80 synuclein alpha Homo sapiens 12-27 33664298-0 2021 Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth. Iron 69-73 synuclein alpha Homo sapiens 13-28 33664298-5 2021 In the excised SNCA-knockout xenografts, TfR1 decreased 3.3-fold, ferritin increased 6.2-fold, the divalent metal ion transporter 1 (DMT1) increased threefold, and the iron exporter ferroportin (FPN1) decreased twofold relative to control xenografts. Iron 168-172 synuclein alpha Homo sapiens 15-19 33664298-7 2021 Collectively, depletion of alpha-syn in SK-Mel-28 cells dysregulates cellular iron metabolism, especially in xenografts, yielding melanoma cells that are deficient in TfR1 and FPN1, that accumulate ferric iron and ferritin, and that undergo apoptosis relative to control cells expressing alpha-syn. Iron 78-82 synuclein alpha Homo sapiens 27-36 33035800-2 2020 Rep1 polymorphism in the promotor region of SNCA is associated with risk of Parkinson"s disease, however its association with RLS and iron status is unclear. Iron 134-138 synuclein alpha Homo sapiens 44-48 33096655-3 2020 Iron deposits are present in the core of Lewy bodies, and there are reports suggesting that divalent metal ions including Cu2+ and Fe2+ enhance the aggregation of alpha-Syn. Iron 0-4 synuclein alpha Homo sapiens 163-172 33096655-7 2020 Research over the past decade has shown that alpha-Syn has iron import functions with an ability to oxidize the Fe3+ form of iron to Fe2+ to facilitate its entry into cells. Iron 59-63 synuclein alpha Homo sapiens 45-54 33096655-7 2020 Research over the past decade has shown that alpha-Syn has iron import functions with an ability to oxidize the Fe3+ form of iron to Fe2+ to facilitate its entry into cells. Iron 125-129 synuclein alpha Homo sapiens 45-54 32318880-5 2020 Perhaps in the early diseased state, overexpression or mutation of alpha-synuclein/ferrireductase invokes the dyshomeostasis of iron (III)/(II) only, while in advanced stages, accumulation of iron in particular areas of the brain follows. Iron 128-132 synuclein alpha Homo sapiens 67-82 32379419-0 2020 alpha-Synuclein regulates iron homeostasis via preventing parkin-mediated DMT1 ubiquitylation in Parkinson"s disease models. Iron 26-30 synuclein alpha Homo sapiens 0-15 32379419-2 2020 alpha-synuclein (alpha-Syn) serves as a ferrireductase and iron-binding protein which is supposed to be linked with iron metabolism, little is known how alpha-Syn affects iron homeostasis in PD. Iron 59-63 synuclein alpha Homo sapiens 0-15 32379419-2 2020 alpha-synuclein (alpha-Syn) serves as a ferrireductase and iron-binding protein which is supposed to be linked with iron metabolism, little is known how alpha-Syn affects iron homeostasis in PD. Iron 59-63 synuclein alpha Homo sapiens 17-26 32379419-2 2020 alpha-synuclein (alpha-Syn) serves as a ferrireductase and iron-binding protein which is supposed to be linked with iron metabolism, little is known how alpha-Syn affects iron homeostasis in PD. Iron 116-120 synuclein alpha Homo sapiens 0-15 32379419-2 2020 alpha-synuclein (alpha-Syn) serves as a ferrireductase and iron-binding protein which is supposed to be linked with iron metabolism, little is known how alpha-Syn affects iron homeostasis in PD. Iron 116-120 synuclein alpha Homo sapiens 17-26 32379419-2 2020 alpha-synuclein (alpha-Syn) serves as a ferrireductase and iron-binding protein which is supposed to be linked with iron metabolism, little is known how alpha-Syn affects iron homeostasis in PD. Iron 116-120 synuclein alpha Homo sapiens 0-15 32379419-2 2020 alpha-synuclein (alpha-Syn) serves as a ferrireductase and iron-binding protein which is supposed to be linked with iron metabolism, little is known how alpha-Syn affects iron homeostasis in PD. Iron 116-120 synuclein alpha Homo sapiens 17-26 32318880-5 2020 Perhaps in the early diseased state, overexpression or mutation of alpha-synuclein/ferrireductase invokes the dyshomeostasis of iron (III)/(II) only, while in advanced stages, accumulation of iron in particular areas of the brain follows. Iron 192-196 synuclein alpha Homo sapiens 67-82 32104855-0 2020 Iron-mediated interaction of alpha synuclein with lipid raft model membranes. Iron 0-4 synuclein alpha Homo sapiens 29-44 32380365-9 2020 When treated with DFO and NAC for iron chelation and antioxidation, the level of HIF-1a and related cytokines could decrease. Iron 34-38 synuclein alpha Homo sapiens 26-29 32025811-4 2020 Here, we describe existing findings regarding the interaction of iron with neuromelanin and alpha synuclein, the iron deposition in experimental animal model of PD and sporadic and familial PD patients, and the treatment option involving the use of iron chelators for targeting the aberration of iron level in brain. Iron 65-69 synuclein alpha Homo sapiens 75-107 32108853-6 2020 Our results tend to suggest that iron inactivates Parkin in SH-SY5Y cells and thereby inhibits the proteasomal degradation of alpha-synuclein, and the accumulated alpha-synuclein causes mitochondrial dysfunction and cell death. Iron 33-37 synuclein alpha Homo sapiens 163-178 32210768-14 2020 Following the up-regulation of ferritin mediated by alpha-syn, hepcidin-to-ferritin levels were indicative of modulatory effects in alpha-syn-treated astrocytes with altered iron status. Iron 174-178 synuclein alpha Homo sapiens 132-141 32108853-0 2020 Interaction of alpha-synuclein and Parkin in iron toxicity on SH-SY5Y cells: implications in the pathogenesis of Parkinson"s disease. Iron 45-49 synuclein alpha Homo sapiens 15-30 32108853-2 2020 This study has demonstrated that iron in varying concentrations (up to 400 microM) causes an increase in alpha-synuclein content in SH-SY5Y cells associated with mitochondrial depolarization, decreased cellular ATP content and loss of cell viability during incubation up to 96 h. Knocking-down alpha-synuclein expression prevents cytotoxic actions of iron, which can also be prevented by cyclosporine A (a blocker of mitochondrial permeability transition pore). Iron 33-37 synuclein alpha Homo sapiens 105-120 32108853-2 2020 This study has demonstrated that iron in varying concentrations (up to 400 microM) causes an increase in alpha-synuclein content in SH-SY5Y cells associated with mitochondrial depolarization, decreased cellular ATP content and loss of cell viability during incubation up to 96 h. Knocking-down alpha-synuclein expression prevents cytotoxic actions of iron, which can also be prevented by cyclosporine A (a blocker of mitochondrial permeability transition pore). Iron 33-37 synuclein alpha Homo sapiens 294-309 32108853-2 2020 This study has demonstrated that iron in varying concentrations (up to 400 microM) causes an increase in alpha-synuclein content in SH-SY5Y cells associated with mitochondrial depolarization, decreased cellular ATP content and loss of cell viability during incubation up to 96 h. Knocking-down alpha-synuclein expression prevents cytotoxic actions of iron, which can also be prevented by cyclosporine A (a blocker of mitochondrial permeability transition pore). Iron 351-355 synuclein alpha Homo sapiens 105-120 32108853-3 2020 These results indicate that iron cytotoxicity is mediated by alpha-synuclein acting on mitochondria. Iron 28-32 synuclein alpha Homo sapiens 61-76 32108853-6 2020 Our results tend to suggest that iron inactivates Parkin in SH-SY5Y cells and thereby inhibits the proteasomal degradation of alpha-synuclein, and the accumulated alpha-synuclein causes mitochondrial dysfunction and cell death. Iron 33-37 synuclein alpha Homo sapiens 126-141 31912279-5 2020 At a molecular level, alpha-synuclein regulates dopamine and iron transport with PD-associated mutations in this protein causing functional disruption to these processes. Iron 61-65 synuclein alpha Homo sapiens 22-37 31233777-3 2019 The direct structural links between iron and alpha-synuclein suggest that structural reorganization provokes alpha-synuclein conformational change. Iron 36-40 synuclein alpha Homo sapiens 45-60 31900363-6 2020 Fortuitously, the SNCA mRNA has a structured iron-responsive element (IRE) in its 5" untranslated region (5" UTR) that controls its translation. Iron 45-49 synuclein alpha Homo sapiens 18-22 31658742-2 2019 Synchrotron X-ray techniques, coupled with ultrahigh-resolution mass spectrometry, have been applied to study iron and copper interactions with amyloid beta (1-42) or alpha-synuclein. Iron 110-114 synuclein alpha Homo sapiens 167-182 31233777-3 2019 The direct structural links between iron and alpha-synuclein suggest that structural reorganization provokes alpha-synuclein conformational change. Iron 36-40 synuclein alpha Homo sapiens 109-124 31233777-4 2019 Iron post-transcriptionally regulates alpha-synuclein synthesis in the presence of iron-responsive element. Iron 0-4 synuclein alpha Homo sapiens 38-53 31233777-4 2019 Iron post-transcriptionally regulates alpha-synuclein synthesis in the presence of iron-responsive element. Iron 83-87 synuclein alpha Homo sapiens 38-53 31233777-5 2019 Increased oxidative/nitrative stress induced by iron is believed to be involved in the post-translational modulation of alpha-synuclein. Iron 48-52 synuclein alpha Homo sapiens 120-135 31233777-6 2019 Iron modulates proteolytic pathways and therefore participates in the regulation of alpha-synuclein levels. Iron 0-4 synuclein alpha Homo sapiens 84-99 31233777-8 2019 Finally, alpha-synuclein might regulate iron metabolism through its ferrireductase activity. Iron 40-44 synuclein alpha Homo sapiens 9-24 31233777-9 2019 A prominent role of alpha-synuclein in iron homeostasis is involved in the uptake of transferrin-Fe. Iron 39-43 synuclein alpha Homo sapiens 20-35 31233777-9 2019 A prominent role of alpha-synuclein in iron homeostasis is involved in the uptake of transferrin-Fe. Iron 97-99 synuclein alpha Homo sapiens 20-35 31417259-0 2019 alpha-synuclein interaction with zero-valent iron nanoparticles accelerates structural rearrangement into amyloid-susceptible structure with increased cytotoxic tendency. Iron 45-49 synuclein alpha Homo sapiens 0-15 31447651-1 2019 An imbalance of iron metabolism with consecutive aggregation of alpha-synuclein and axonal degeneration of neurons has been postulated as the main pathological feature in the development of Parkinson"s disease (PD). Iron 16-20 synuclein alpha Homo sapiens 64-79 30536543-8 2019 Based on a few experimental studies, the combination of iron chelators with some anti-oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. Iron 56-60 synuclein alpha Homo sapiens 106-109 31377220-7 2019 High levels of Cu, Mn and Fe participate in the formation alpha-synuclein aggregates in intracellular inclusions, called Lewy Body, that result in synaptic dysfunction and interruption of axonal transport. Iron 26-28 synuclein alpha Homo sapiens 58-73 30554085-1 2019 In Parkinson"s disease (PD), iron accumulation in the substantia nigra (SN) exacerbates oxidative stress and alpha-synuclein aggregation, leading to neuronal death. Iron 29-33 synuclein alpha Homo sapiens 109-124 31235814-0 2019 Iron-mediated aggregation and toxicity in a novel neuronal cell culture model with inducible alpha-synuclein expression. Iron 0-4 synuclein alpha Homo sapiens 93-108 30797969-0 2019 Iron-induced oxidative stress contributes to alpha-synuclein phosphorylation and up-regulation via polo-like kinase 2 and casein kinase 2. Iron 0-4 synuclein alpha Homo sapiens 45-60 30797969-4 2019 We previously reported iron up-regulated alpha-synuclein mRNA levels and induced alpha-synuclein aggregation. Iron 23-27 synuclein alpha Homo sapiens 41-56 30797969-4 2019 We previously reported iron up-regulated alpha-synuclein mRNA levels and induced alpha-synuclein aggregation. Iron 23-27 synuclein alpha Homo sapiens 81-96 30797969-5 2019 In the present study, we aimed to investigate whether and how phosphorylation was involved in iron-induced alpha-synuclein regulations. Iron 94-98 synuclein alpha Homo sapiens 107-122 30797969-7 2019 Over-expression of CK2 or PLK2 induced pS129 alpha-synuclein up-regulation and inhibitors of CK2 or PLK2 could suppress iron-induced alpha-synuclein phosphorylation. Iron 120-124 synuclein alpha Homo sapiens 45-60 30797969-7 2019 Over-expression of CK2 or PLK2 induced pS129 alpha-synuclein up-regulation and inhibitors of CK2 or PLK2 could suppress iron-induced alpha-synuclein phosphorylation. Iron 120-124 synuclein alpha Homo sapiens 133-148 30797969-8 2019 Antioxidant NAC could fully block iron-induced upregulation of CK2, PLK2 and pS129 alpha-synuclein levels, indicating oxidative stress plays a critical role in iron-induced alpha-synuclein phosphorylation. Iron 34-38 synuclein alpha Homo sapiens 12-15 30266679-2 2019 Proteins such as alpha-synuclein, tau and amyloid precursor protein that are pathologically associated with neurodegeneration are involved in molecular crosstalk with iron homeostatic proteins. Iron 167-171 synuclein alpha Homo sapiens 17-32 30797969-8 2019 Antioxidant NAC could fully block iron-induced upregulation of CK2, PLK2 and pS129 alpha-synuclein levels, indicating oxidative stress plays a critical role in iron-induced alpha-synuclein phosphorylation. Iron 34-38 synuclein alpha Homo sapiens 83-98 30797969-8 2019 Antioxidant NAC could fully block iron-induced upregulation of CK2, PLK2 and pS129 alpha-synuclein levels, indicating oxidative stress plays a critical role in iron-induced alpha-synuclein phosphorylation. Iron 34-38 synuclein alpha Homo sapiens 173-188 30797969-8 2019 Antioxidant NAC could fully block iron-induced upregulation of CK2, PLK2 and pS129 alpha-synuclein levels, indicating oxidative stress plays a critical role in iron-induced alpha-synuclein phosphorylation. Iron 160-164 synuclein alpha Homo sapiens 12-15 30797969-8 2019 Antioxidant NAC could fully block iron-induced upregulation of CK2, PLK2 and pS129 alpha-synuclein levels, indicating oxidative stress plays a critical role in iron-induced alpha-synuclein phosphorylation. Iron 160-164 synuclein alpha Homo sapiens 173-188 30797969-9 2019 However, iron-induced alpha-synuclein up-regulation could only be partially blocked by CK2/PLK2 inhibitor or NAC. Iron 9-13 synuclein alpha Homo sapiens 22-37 30797969-9 2019 However, iron-induced alpha-synuclein up-regulation could only be partially blocked by CK2/PLK2 inhibitor or NAC. Iron 9-13 synuclein alpha Homo sapiens 109-112 30797969-10 2019 These findings demonstrate that iron-induced oxidative stress is largely responsible for alpha-synuclein phosphorylation and upregulation via CK2 and PLK2, and alpha-synuclein upregulation is not fully phosphorylation-dependent. Iron 32-36 synuclein alpha Homo sapiens 89-104 30590010-5 2019 In addition, iron directly interacts with alpha-synuclein in Lewy bodies, which are primarily digested through the autophagy-lysosome pathway. Iron 13-17 synuclein alpha Homo sapiens 42-57 30723395-4 2019 The process of misfolding and aggregation of neuronal proteins such as alpha-synuclein, Tau, amyloid beta (Abeta), TDP-43 or SOD1 is a common hallmark of many neurodegenerative disorders and iron has been shown to facilitate protein aggregation. Iron 191-195 synuclein alpha Homo sapiens 71-86 30465671-7 2019 Most studies investigating the relationship of Cu, Fe and Zn with alpha-synuclein have relied on the use of recombinant protein and there is little evidence that the interaction between metals and alpha-synuclein are physiologically relevant. Iron 51-53 synuclein alpha Homo sapiens 66-81 30465671-9 2019 In addition, we examined the ability of dityrosine cross-linked alpha-synuclein oligomers to bind Cu, Fe and Zn. Iron 102-104 synuclein alpha Homo sapiens 64-79 30791479-3 2019 Several factors have been found to trigger alpha-syn aggregation, including raised calcium, iron, and copper. Iron 92-96 synuclein alpha Homo sapiens 43-52 29679389-2 2019 Natural resistance-associated macrophage protein-1 (Nramp1) was previously shown to contribute to the degradation of extracellular alpha-synuclein in microglia under conditions of iron overload. Iron 180-184 synuclein alpha Homo sapiens 131-146 31456205-5 2019 Iron is believed to modulate alpha-synuclein synthesis, post-translational modification, and aggregation. Iron 0-4 synuclein alpha Homo sapiens 29-44 30342981-0 2019 Rosmarinic acid protects against MPTP-induced toxicity and inhibits iron-induced alpha-synuclein aggregation. Iron 68-72 synuclein alpha Homo sapiens 81-96 31456205-4 2019 There is emerging evidence on the structural links and functional modulations between iron and alpha-synuclein, and the key player in PD which aggregates in Lewy bodies. Iron 86-90 synuclein alpha Homo sapiens 95-110 29681846-0 2018 High Dietary Iron Supplement Induces the Nigrostriatal Dopaminergic Neurons Lesion in Transgenic Mice Expressing Mutant A53T Human Alpha-Synuclein. Iron 13-17 synuclein alpha Homo sapiens 131-146 30342981-5 2019 Results showed that iron could induce a decrease in the mitochondrial transmembrane potential and result in alpha-synuclein aggregation in the SK-N-SH cells, which could be restored by RA pretreatment. Iron 20-24 synuclein alpha Homo sapiens 108-123 30342981-6 2019 Further results showed RA pretreatment could inhibit iron-induced alpha-synuclein aggregation by up-regulating hemeoxygenase-1 (HO-1). Iron 53-57 synuclein alpha Homo sapiens 66-81 30342981-7 2019 In addition, iron could increase the mRNA levels of alpha-synuclein via iron responsive element/iron regulatory protein (IRE/IRP) system. Iron 13-17 synuclein alpha Homo sapiens 52-67 30342981-7 2019 In addition, iron could increase the mRNA levels of alpha-synuclein via iron responsive element/iron regulatory protein (IRE/IRP) system. Iron 72-76 synuclein alpha Homo sapiens 52-67 30342981-9 2019 These results indicated that RA protected against iron-induced alpha-synuclein aggregation by up-regulating HO-1 and inhibiting alpha-synuclein expression. Iron 50-54 synuclein alpha Homo sapiens 63-78 30342981-9 2019 These results indicated that RA protected against iron-induced alpha-synuclein aggregation by up-regulating HO-1 and inhibiting alpha-synuclein expression. Iron 50-54 synuclein alpha Homo sapiens 128-143 29452354-5 2018 We discovered that alpha-syn expression phenocopies the high iron condition: under the low iron condition (<1 microM), alpha-syn inhibits Snx3-retromer-mediated recycling of Fet3/Ftr1 and instead shunts Fet3/Ftr1 into the multivesicular body pathway to the vacuole. Iron 91-95 synuclein alpha Homo sapiens 119-128 29452354-7 2018 In C. elegans, transgenic worms expressing alpha-syn exhibit an age-dependent degeneration of dopaminergic neurons that is partially rescued by the iron chelator desferoxamine. Iron 148-152 synuclein alpha Homo sapiens 43-52 29452354-8 2018 This implies that alpha-syn-expressing dopaminergic neurons are susceptible to changes in iron neurotoxicity with age, whereby excess iron enhances alpha-syn-induced neurodegeneration. Iron 90-94 synuclein alpha Homo sapiens 18-27 29452354-8 2018 This implies that alpha-syn-expressing dopaminergic neurons are susceptible to changes in iron neurotoxicity with age, whereby excess iron enhances alpha-syn-induced neurodegeneration. Iron 134-138 synuclein alpha Homo sapiens 18-27 29452354-8 2018 This implies that alpha-syn-expressing dopaminergic neurons are susceptible to changes in iron neurotoxicity with age, whereby excess iron enhances alpha-syn-induced neurodegeneration. Iron 134-138 synuclein alpha Homo sapiens 148-157 29452354-9 2018 In vivo genetic analysis indicates that alpha-syn dysregulates iron homeostasis in worm dopaminergic neurons, possibly by inhibiting SNX-3-mediated recycling of a membrane-bound ortholog of Cp (F21D5.3), the iron exporter ferroportin (FPN1.1), or both. Iron 63-67 synuclein alpha Homo sapiens 40-49 29452354-9 2018 In vivo genetic analysis indicates that alpha-syn dysregulates iron homeostasis in worm dopaminergic neurons, possibly by inhibiting SNX-3-mediated recycling of a membrane-bound ortholog of Cp (F21D5.3), the iron exporter ferroportin (FPN1.1), or both. Iron 208-212 synuclein alpha Homo sapiens 40-49 29452354-1 2018 We probed the role of alpha-synuclein (alpha-syn) in modulating sorting nexin 3 (Snx3)-retromer-mediated recycling of iron transporters in Saccharomyces cerevisiae and Caenorhabditis elegans. Iron 118-122 synuclein alpha Homo sapiens 22-31 29452354-5 2018 We discovered that alpha-syn expression phenocopies the high iron condition: under the low iron condition (<1 microM), alpha-syn inhibits Snx3-retromer-mediated recycling of Fet3/Ftr1 and instead shunts Fet3/Ftr1 into the multivesicular body pathway to the vacuole. Iron 61-65 synuclein alpha Homo sapiens 19-28 29452354-5 2018 We discovered that alpha-syn expression phenocopies the high iron condition: under the low iron condition (<1 microM), alpha-syn inhibits Snx3-retromer-mediated recycling of Fet3/Ftr1 and instead shunts Fet3/Ftr1 into the multivesicular body pathway to the vacuole. Iron 61-65 synuclein alpha Homo sapiens 119-128 29608844-0 2018 Iron Redox Chemistry Promotes Antiparallel Oligomerization of alpha-Synuclein. Iron 0-4 synuclein alpha Homo sapiens 62-77 28592304-0 2017 Post translational changes to alpha-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson"s disease. Iron 54-58 synuclein alpha Homo sapiens 30-45 29076411-4 2018 In particular, copper, zinc and iron are recognized to influence the biochemistry of proteins involved in neurodegeneration (for instance Abeta and alpha-synuclein), as well as those playing a crucial role in neuronal development and efficiency (neurotrophins). Iron 32-36 synuclein alpha Homo sapiens 148-163 28476637-2 2017 In this study, concomitant with the accumulation of iron and oligomeric alpha-synuclein, higher expression of a lysosomal iron transporter, natural resistance-associated macrophage protein-1 (Nramp1), was observed in microglia in post-mortem striatum of sporadic PD patients. Iron 122-126 synuclein alpha Homo sapiens 72-87 28476637-3 2017 Using Nramp1-deficient macrophage (RAW264.7) and microglial (BV-2) cells as in-vitro models, iron exposure significantly reduced the degradation rate of the administered human alpha-synuclein oligomers, which can be restored by the expression of the wild-type, but not mutant (D543N), Nramp1. Iron 93-97 synuclein alpha Homo sapiens 176-191 28476637-4 2017 Likewise, under iron overload condition, mice with functional Nramp1 (DBA/2 and C57BL/6 congenic mice carrying functional Nramp1) had a better ability to degrade infused human alpha-synuclein oligomers than mice with nonfunctional Nramp1 (C57BL/6) in the brain and microglia. Iron 16-20 synuclein alpha Homo sapiens 176-191 28651647-6 2017 Iron accumulation and oxidative stress are able to aggregate some proteins, including Abeta and alpha-synuclein, which play a critical role in Alzheimer"s and Parkinson"s diseases, respectively. Iron 0-4 synuclein alpha Homo sapiens 96-111 29376857-7 2018 Iron converts native alpha-SYN into a beta-sheet conformation and promotes its aggregation either directly or via increasing levels of oxidative stress. Iron 0-4 synuclein alpha Homo sapiens 21-30 29376857-8 2018 Interestingly, alpha-SYN possesses ferrireductase activity and alpha-SYN expression underlies iron mediated translational control via RNA stem loop structures. Iron 94-98 synuclein alpha Homo sapiens 15-24 29376857-8 2018 Interestingly, alpha-SYN possesses ferrireductase activity and alpha-SYN expression underlies iron mediated translational control via RNA stem loop structures. Iron 94-98 synuclein alpha Homo sapiens 63-72 28811225-3 2017 Recently, it has been suggested that alpha-synuclein could cause the enzymatic reduction of iron and a cellular increase in Fe(II) levels. Iron 92-96 synuclein alpha Homo sapiens 37-52 29061112-6 2017 The levels of alpha-Syn, APP and amyloid beta-peptide (Abeta) as well as protein aggregation can be down-regulated by IRPs but are up-regulated in the presence of iron accumulation. Iron 163-167 synuclein alpha Homo sapiens 14-23 28874699-5 2017 Combining laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry, iron and copper were evident at very low levels in regions of alpha-synuclein aggregation. Iron 96-100 synuclein alpha Homo sapiens 158-173 28592304-5 2017 Furthermore, we propose a concept in which acetylation and phosphorylation of alpha-syn modulate endocytic import of iron and vesicle transport of dopamine during normal physiology. Iron 117-121 synuclein alpha Homo sapiens 78-87 28592304-6 2017 Disregulated phosphorylation and oxidation of alpha-syn mediate iron and dopamine dependent oxidative stress through impaired cellular location and increase propensity for alpha-syn aggregation. Iron 64-68 synuclein alpha Homo sapiens 46-55 28452474-3 2017 Previous work has suggested that alpha-synuclein can catalyze the reduction of iron as a ferrireductase. Iron 79-83 synuclein alpha Homo sapiens 33-48 27424009-8 2017 The effects caused by iron (500 microM) were mostly independent of alpha-syn expression and triggered different antioxidant responses to possibly counterbalance higher levels of free radicals. Iron 22-26 synuclein alpha Homo sapiens 67-76 28163159-11 2017 Our results indicate that FtMt modulates alpha-synuclein expression at the posttranscriptional level via iron regulation in physiological conditions. Iron 105-109 synuclein alpha Homo sapiens 41-56 28236214-9 2017 Mutant Atx3 and alpha-Syn also potentiated altered redox status induced by iron and rotenone, a hint to how these proteins might influence neuronal dysfunction under pro-oxidant conditions. Iron 75-79 synuclein alpha Homo sapiens 16-25 28424751-3 2017 The excess iron promotes Parkin and alpha-synuclein aggregation in the neurons. Iron 11-15 synuclein alpha Homo sapiens 36-51 28138322-6 2017 After treatment with rapamycin, the iron loading-induced increase in the alpha-synuclein level was significantly reversed and ROS generation was alleviated in both cultured neurons and SH-SY5Y cells. Iron 36-40 synuclein alpha Homo sapiens 73-88 28138322-7 2017 These results indicate that the inhibition of autophagy is critical for the pathological alterations in alpha-synuclein induced by iron loading. Iron 131-135 synuclein alpha Homo sapiens 104-119 28138322-9 2017 Together, our study shows that autophagy dysfunction contributes to iron-induced alpha-synuclein pathology. Iron 68-72 synuclein alpha Homo sapiens 81-96 28138322-0 2017 Iron Deposition Leads to Neuronal alpha-Synuclein Pathology by Inducing Autophagy Dysfunction. Iron 0-4 synuclein alpha Homo sapiens 34-49 28138322-3 2017 Using primary dopaminergic neurons and SH-SY5Y cells cultured in vitro, we observed that iron loading increased alpha-synuclein and reactive oxygen species (ROS) levels in these cells but did not affect the intracellular alpha-synuclein mRNA levels. Iron 89-93 synuclein alpha Homo sapiens 112-127 27343690-9 2016 Interestingly, exposure to exogenous iron increased membrane association and co-localization of alpha-syn with TfR, supporting its role in iron uptake by the Tf/TfR complex. Iron 37-41 synuclein alpha Homo sapiens 96-105 28731447-2 2017 The neurotoxicity of alpha-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Iron 46-50 synuclein alpha Homo sapiens 21-30 28731447-2 2017 The neurotoxicity of alpha-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Iron 52-54 synuclein alpha Homo sapiens 21-30 28731447-6 2017 Moderate (~2-fold) increase in alpha-Syn expression in neural lineage progenitor cells (NPC) derived from induced pluripotent human stem cells (iPSCs) or differentiated SHSY-5Y cells caused DNA strand breaks in the nuclear genome, which was further enhanced synergistically by Fe salts. Iron 277-279 synuclein alpha Homo sapiens 31-40 28731447-9 2017 Consistent with this finding, a marked increase in Fe-dependent DNA breaks was observed in NPCs from a PD patient-derived iPSC line harboring triplication of the SNCA gene. Iron 51-53 synuclein alpha Homo sapiens 162-166 27769419-2 2016 The interplay between aberrations in the structural organization and elemental composition of SN neuron bodies has recently gained in importance as selected metals: Fe, Cu, Zn, Ca were found to trigger oxidative-stress-mediated aberration in their molecular assembly due to concomitant protein (alpha-synuclein, tau-protein) aggregation, gliosis and finally oxidative stress. Iron 165-167 synuclein alpha Homo sapiens 295-310 26545340-3 2016 Indeed, many proteins initially characterized in those diseases such as amyloid-beta protein, alpha-synuclein, and huntingtin have been linked to iron neurochemistry. Iron 146-150 synuclein alpha Homo sapiens 94-109 27343690-9 2016 Interestingly, exposure to exogenous iron increased membrane association and co-localization of alpha-syn with TfR, supporting its role in iron uptake by the Tf/TfR complex. Iron 139-143 synuclein alpha Homo sapiens 96-105 26235306-5 2015 Moreover, the acute toxicity of the three NAC effluents significantly decreased after treatment with ZVI. Iron 101-104 synuclein alpha Homo sapiens 42-45 26769358-4 2016 Recent studies showed that mutant and wild-type alpha-synuclein may have differential interaction with iron and mutant alpha-synuclein toxicity could be preferentially exacerbated by iron. Iron 103-107 synuclein alpha Homo sapiens 48-63 26769358-4 2016 Recent studies showed that mutant and wild-type alpha-synuclein may have differential interaction with iron and mutant alpha-synuclein toxicity could be preferentially exacerbated by iron. Iron 183-187 synuclein alpha Homo sapiens 48-63 26769358-5 2016 We hence hypothesized that iron overload could selectively influence mutant alpha-synuclein toxicity and disease phenotypes. Iron 27-31 synuclein alpha Homo sapiens 76-91 26769358-7 2016 We showed that iron treatment induced similar reduction of survival rate in all flies but induced a more severe motor decline in A53T and A30P mutant alpha-synuclein expressing flies, suggesting interaction between mutant alpha-synuclein and iron. Iron 15-19 synuclein alpha Homo sapiens 150-165 26769358-7 2016 We showed that iron treatment induced similar reduction of survival rate in all flies but induced a more severe motor decline in A53T and A30P mutant alpha-synuclein expressing flies, suggesting interaction between mutant alpha-synuclein and iron. Iron 15-19 synuclein alpha Homo sapiens 222-237 26769358-8 2016 Although no significant difference in total head iron content was found among these flies, we demonstrated that iron treatment induced selective DA neuron loss in motor-related PPM3 cluster only in the flies that express A53T and A30P mutant alpha-synuclein. Iron 112-116 synuclein alpha Homo sapiens 242-257 26769358-9 2016 We provided the first in vivo evidence that iron overload could induce distinctive neuropathology and disease phenotypes in mutant but not WT alpha-synuclein expressing flies, providing insights to the cause of clinical features selectively exhibited by mutant alpha-synuclein carriers. Iron 44-48 synuclein alpha Homo sapiens 261-276 25833099-0 2016 alpha-Synuclein Over-Expression Induces Increased Iron Accumulation and Redistribution in Iron-Exposed Neurons. Iron 50-54 synuclein alpha Homo sapiens 0-15 25833099-0 2016 alpha-Synuclein Over-Expression Induces Increased Iron Accumulation and Redistribution in Iron-Exposed Neurons. Iron 90-94 synuclein alpha Homo sapiens 0-15 25833099-2 2016 Metal to protein binding assays have shown that alpha-synuclein can bind iron in vitro; therefore, we hypothesized that iron content and iron distribution could be modified in cellulo, in cells over-expressing alpha-synuclein. Iron 73-77 synuclein alpha Homo sapiens 48-63 25833099-2 2016 Metal to protein binding assays have shown that alpha-synuclein can bind iron in vitro; therefore, we hypothesized that iron content and iron distribution could be modified in cellulo, in cells over-expressing alpha-synuclein. Iron 73-77 synuclein alpha Homo sapiens 210-225 25833099-2 2016 Metal to protein binding assays have shown that alpha-synuclein can bind iron in vitro; therefore, we hypothesized that iron content and iron distribution could be modified in cellulo, in cells over-expressing alpha-synuclein. Iron 120-124 synuclein alpha Homo sapiens 48-63 25833099-2 2016 Metal to protein binding assays have shown that alpha-synuclein can bind iron in vitro; therefore, we hypothesized that iron content and iron distribution could be modified in cellulo, in cells over-expressing alpha-synuclein. Iron 120-124 synuclein alpha Homo sapiens 210-225 25833099-2 2016 Metal to protein binding assays have shown that alpha-synuclein can bind iron in vitro; therefore, we hypothesized that iron content and iron distribution could be modified in cellulo, in cells over-expressing alpha-synuclein. Iron 120-124 synuclein alpha Homo sapiens 48-63 25833099-2 2016 Metal to protein binding assays have shown that alpha-synuclein can bind iron in vitro; therefore, we hypothesized that iron content and iron distribution could be modified in cellulo, in cells over-expressing alpha-synuclein. Iron 120-124 synuclein alpha Homo sapiens 210-225 25833099-4 2016 We show that, in neurons exposed to excess iron, the mere over-expression of human alpha-synuclein results in increased levels of intracellular iron and in iron redistribution from the cytoplasm to the perinuclear region within alpha-synuclein-rich inclusions. Iron 43-47 synuclein alpha Homo sapiens 83-98 25833099-4 2016 We show that, in neurons exposed to excess iron, the mere over-expression of human alpha-synuclein results in increased levels of intracellular iron and in iron redistribution from the cytoplasm to the perinuclear region within alpha-synuclein-rich inclusions. Iron 43-47 synuclein alpha Homo sapiens 228-243 25833099-4 2016 We show that, in neurons exposed to excess iron, the mere over-expression of human alpha-synuclein results in increased levels of intracellular iron and in iron redistribution from the cytoplasm to the perinuclear region within alpha-synuclein-rich inclusions. Iron 144-148 synuclein alpha Homo sapiens 83-98 25833099-4 2016 We show that, in neurons exposed to excess iron, the mere over-expression of human alpha-synuclein results in increased levels of intracellular iron and in iron redistribution from the cytoplasm to the perinuclear region within alpha-synuclein-rich inclusions. Iron 144-148 synuclein alpha Homo sapiens 83-98 26284970-5 2015 A strong correlation between Cu-/Mn-levels as well as Fe-/Mn-levels was observed in alphaSyn-overexpressing cells. Iron 54-56 synuclein alpha Homo sapiens 84-92 24954801-1 2015 Impaired cellular homeostasis of metals, particularly of Cu, Fe and Mn may trigger neurodegeneration through various mechanisms, notably induction of oxidative stress, promotion of alpha-synuclein aggregation and fibril formation, activation of microglial cells leading to inflammation and impaired production of metalloproteins. Iron 61-63 synuclein alpha Homo sapiens 181-196 25648629-7 2015 Here we give a brief overview on alphaSyn pathology and the role of metals in the brain and then address in more detail the interaction of alphaSyn with three disease-relevant transition metals, iron (Fe), copper (Cu) and manganese (Mn). Iron 195-199 synuclein alpha Homo sapiens 139-147 25648629-7 2015 Here we give a brief overview on alphaSyn pathology and the role of metals in the brain and then address in more detail the interaction of alphaSyn with three disease-relevant transition metals, iron (Fe), copper (Cu) and manganese (Mn). Iron 201-203 synuclein alpha Homo sapiens 139-147 26521482-2 2015 Alpha-synuclein aggregation is often accompanied by abnormal accumulation of iron, indicating that there is a certain link between iron and alpha-synuclein aggregation. Iron 77-81 synuclein alpha Homo sapiens 0-15 26521482-2 2015 Alpha-synuclein aggregation is often accompanied by abnormal accumulation of iron, indicating that there is a certain link between iron and alpha-synuclein aggregation. Iron 77-81 synuclein alpha Homo sapiens 140-155 26521482-2 2015 Alpha-synuclein aggregation is often accompanied by abnormal accumulation of iron, indicating that there is a certain link between iron and alpha-synuclein aggregation. Iron 131-135 synuclein alpha Homo sapiens 0-15 26521482-2 2015 Alpha-synuclein aggregation is often accompanied by abnormal accumulation of iron, indicating that there is a certain link between iron and alpha-synuclein aggregation. Iron 131-135 synuclein alpha Homo sapiens 140-155 26521482-3 2015 Iron promotes alpha-synuclein aggregation by increasing its synthesis and decreasing its degradation. Iron 0-4 synuclein alpha Homo sapiens 14-29 26521482-4 2015 Also, alpha-synuclein regulates iron metabolism through its ferrireductase activity. Iron 32-36 synuclein alpha Homo sapiens 6-21 25006697-4 2014 Specifically, we will focus on heme peroxidases, metallo-beta-lactamases, alpha-synuclein and ligase ribozymes to show how this approach is capable of describing the catalytic and/or structural role played by transition (Fe, Zn or Cu) and main group (Mg) metals. Iron 221-223 synuclein alpha Homo sapiens 74-89 24475238-6 2014 We report that in human Parkinson"s brains increased iron concentrations in the substantia nigra are associated with upregulated levels of Ndfip1 in dopaminergic neurons containing alpha-synuclein deposits. Iron 53-57 synuclein alpha Homo sapiens 181-196 24256246-4 2013 It has been suggested recently that alpha-synuclein is able to reduce iron using copper as its catalytic centre. Iron 70-74 synuclein alpha Homo sapiens 36-51 23454680-9 2013 Inhibition of Nrf2/HO-1 leads to more alpha-syn aggregation and greater toxicity induced by iron, creating a vicious cycle of iron accumulation, alpha-syn aggregation and HO-1 disruption in PD. Iron 92-96 synuclein alpha Homo sapiens 145-154 23376471-2 2013 The elevated iron levels observed in the substantia nigra of PD subjects have been suggested to incite the generation of reactive oxygen species and intracellular alpha-synuclein aggregation, terminating in the oxidative neuronal destruction of this brain area. Iron 13-17 synuclein alpha Homo sapiens 163-178 23454680-2 2013 Iron is also believed to serve as a major contributor by inducing oxidative stress and alpha-syn aggregation. Iron 0-4 synuclein alpha Homo sapiens 87-96 23454680-9 2013 Inhibition of Nrf2/HO-1 leads to more alpha-syn aggregation and greater toxicity induced by iron, creating a vicious cycle of iron accumulation, alpha-syn aggregation and HO-1 disruption in PD. Iron 126-130 synuclein alpha Homo sapiens 38-47 23454680-3 2013 Here, we report that down-regulation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) may contribute to iron-induced alpha-syn aggregation. Iron 128-132 synuclein alpha Homo sapiens 141-150 22754573-5 2012 This additional free-iron has the capacity to generate reactive oxygen species, promote the aggregation of alpha-synuclein protein, and exacerbate or even cause neurodegeneration. Iron 21-25 synuclein alpha Homo sapiens 107-122 22581044-4 2012 Interestingly, on the basis of the presence of a putative iron responsive element in the 5"-UTR, it has been suggested that there is a possible iron-dependent translational control of human alpha-synuclein mRNA. Iron 58-62 synuclein alpha Homo sapiens 190-205 22581044-4 2012 Interestingly, on the basis of the presence of a putative iron responsive element in the 5"-UTR, it has been suggested that there is a possible iron-dependent translational control of human alpha-synuclein mRNA. Iron 144-148 synuclein alpha Homo sapiens 190-205 22581044-5 2012 Considering the similarity between the sequences present in human alpha-synuclein mRNA and the ferritin iron responsive element, we postulated that iron deficiency would decrease the translation of alpha-synuclein mRNA. Iron 104-108 synuclein alpha Homo sapiens 198-213 22581044-6 2012 Here we used HEK293 cells treated with iron chelator deferoxamine or ferric ammonium citrate to verify the possible iron-dependent translational control of human alpha-synuclein biosynthesis. Iron 39-43 synuclein alpha Homo sapiens 162-177 22581044-6 2012 Here we used HEK293 cells treated with iron chelator deferoxamine or ferric ammonium citrate to verify the possible iron-dependent translational control of human alpha-synuclein biosynthesis. Iron 116-120 synuclein alpha Homo sapiens 162-177 22581044-8 2012 Our data demonstrate that human alpha-synuclein expression is regulated by iron mainly at the translational level. Iron 75-79 synuclein alpha Homo sapiens 32-47 22581044-9 2012 This result not only supports a role for iron in the translational control of alpha-synuclein expression, but also suggests that iron chelation may be a valid approach to control alpha-synuclein levels in the brain. Iron 41-45 synuclein alpha Homo sapiens 78-93 22581044-9 2012 This result not only supports a role for iron in the translational control of alpha-synuclein expression, but also suggests that iron chelation may be a valid approach to control alpha-synuclein levels in the brain. Iron 129-133 synuclein alpha Homo sapiens 179-194 22500765-3 2012 With the use of confocal single-molecule fluorescence techniques, we demonstrate that small aggregates (oligomers) of alpha-synuclein formed from unbound monomeric species in the presence of organic solvent (DMSO) and iron (Fe(3+)) ions have a high affinity to bind to model membranes, regardless of the lipid-composition or membrane curvature. Iron 218-222 synuclein alpha Homo sapiens 118-133 22500765-3 2012 With the use of confocal single-molecule fluorescence techniques, we demonstrate that small aggregates (oligomers) of alpha-synuclein formed from unbound monomeric species in the presence of organic solvent (DMSO) and iron (Fe(3+)) ions have a high affinity to bind to model membranes, regardless of the lipid-composition or membrane curvature. Iron 224-226 synuclein alpha Homo sapiens 118-133 22581044-0 2012 alpha-Synuclein expression is modulated at the translational level by iron. Iron 70-74 synuclein alpha Homo sapiens 0-15 22581044-1 2012 Several studies have suggested an interaction between alpha-synuclein protein and iron in Parkinson"s disease. Iron 82-86 synuclein alpha Homo sapiens 54-69 22880029-4 2012 In this study, employing a setup for single-channel electrophysiology, we found that addition of iron-induced alpha-synuclein oligomers resulted in quantized and stepwise increases in bilayer conductance indicating insertion of distinct transmembrane pores. Iron 97-101 synuclein alpha Homo sapiens 110-125 22880029-9 2012 Our findings indicate that iron-induced alpha-synuclein oligomers can form a uniform and distinct pore species with characteristic electrophysiological properties. Iron 27-31 synuclein alpha Homo sapiens 40-55 21426349-0 2011 AMPA-receptor-mediated excitatory synaptic transmission is enhanced by iron-induced alpha-synuclein oligomers. Iron 71-75 synuclein alpha Homo sapiens 84-99 22860160-6 2011 In this paper, we sought to map the interactions between the di- and trivalent cations, Cu(II), Pb(II), Fe(II), and Fe(III), and the C-terminal region of alpha-syn encompassing residues 107-140 and to determine how phosphorylation at S129 or Y125 alters the specificity and binding affinity of metals using electrospray ionization-mass spectrometry (ESI-MS) and fluorescence spectroscopy. Iron 104-106 synuclein alpha Homo sapiens 154-163 21598363-0 2011 Photoelectric protein nanofibrils of alpha-synuclein with embedded iron and phthalocyanine tetrasulfonate. Iron 67-71 synuclein alpha Homo sapiens 37-52 21221670-2 2011 Dopaminergic neurons exhibit elevated iron levels that can accelerate toxic SNCA fibril formation. Iron 38-42 synuclein alpha Homo sapiens 76-80 20383623-0 2011 Oxidative stress partially contributes to iron-induced alpha-synuclein aggregation in SK-N-SH cells. Iron 42-46 synuclein alpha Homo sapiens 55-70 20383623-2 2011 As its main component, aggregated alpha-synuclein is presented in the substantia nigra, the same region iron accumulation occurs. Iron 104-108 synuclein alpha Homo sapiens 34-49 20383623-3 2011 In this study, the relationship between iron and alpha-synuclein aggregation was investigated. Iron 40-44 synuclein alpha Homo sapiens 49-64 20383623-7 2011 Due to the predicted iron responsive element (IRE) in the 5"-untranslated region of the human alpha-synuclein mRNA contains, we observed that alpha-synuclein mRNA level was up-regulated in SK-N-SH cells with iron regulatory protein (IRP) knockdown and more alpha-synuclein aggregations were observed in cells. Iron 21-25 synuclein alpha Homo sapiens 94-109 20383623-7 2011 Due to the predicted iron responsive element (IRE) in the 5"-untranslated region of the human alpha-synuclein mRNA contains, we observed that alpha-synuclein mRNA level was up-regulated in SK-N-SH cells with iron regulatory protein (IRP) knockdown and more alpha-synuclein aggregations were observed in cells. Iron 21-25 synuclein alpha Homo sapiens 142-157 20383623-7 2011 Due to the predicted iron responsive element (IRE) in the 5"-untranslated region of the human alpha-synuclein mRNA contains, we observed that alpha-synuclein mRNA level was up-regulated in SK-N-SH cells with iron regulatory protein (IRP) knockdown and more alpha-synuclein aggregations were observed in cells. Iron 21-25 synuclein alpha Homo sapiens 142-157 20383623-8 2011 The results suggest that iron-induced intracellular aggregated alpha-synuclein is partially dependent on oxidative stress and iron might also regulate alpha-synuclein aggregation through the IRE/IRP system. Iron 25-29 synuclein alpha Homo sapiens 63-78 20383623-8 2011 The results suggest that iron-induced intracellular aggregated alpha-synuclein is partially dependent on oxidative stress and iron might also regulate alpha-synuclein aggregation through the IRE/IRP system. Iron 25-29 synuclein alpha Homo sapiens 151-166 20383623-8 2011 The results suggest that iron-induced intracellular aggregated alpha-synuclein is partially dependent on oxidative stress and iron might also regulate alpha-synuclein aggregation through the IRE/IRP system. Iron 126-130 synuclein alpha Homo sapiens 151-166 20690031-6 2011 However, while silencing the expression of alpha-synuclein in SK-N-SH cells with siRNA, iron-induced toxicity could be partially alleviated, indicated by the returned Deltapsi(m) and cell viability and reduced ROS formation compared with that of control. Iron 88-92 synuclein alpha Homo sapiens 43-58 20690031-8 2011 The results suggest that alpha-synuclein aggregation was involved in the toxicity of iron to SK-N-SH neuroblastoma cells. Iron 85-89 synuclein alpha Homo sapiens 25-40 21221670-9 2011 For Posiphen this inhibition was accelerated in the presence of iron, thus providing a known APP-directed lead with potential for use as a SNCA blocker for PD therapy. Iron 64-68 synuclein alpha Homo sapiens 139-143 23934922-4 2011 METHODOLOGY/PRINCIPAL FINDINGS: We investigated the interplay of reactive oxygen species, antioxidants and iron oxidation state in regard to alpha-synuclein aggregation using confocal single particle fluorescence spectroscopy, Phenanthroline spectrometry and thiobarbituric acid reactive substances assay. Iron 107-111 synuclein alpha Homo sapiens 141-156 23934922-8 2011 CONCLUSIONS/SIGNIFICANCE: Our data thus indicate that oxidative stress affects alpha-synuclein aggregation via oxidation of iron to the ferric state. Iron 124-128 synuclein alpha Homo sapiens 79-94 18491043-0 2008 Molecular understanding of copper and iron interaction with alpha-synuclein by fluorescence analysis. Iron 38-42 synuclein alpha Homo sapiens 60-75 20005574-3 2010 The interaction between iron and alpha-syn might have important biological relevance to PD etiology. Iron 24-28 synuclein alpha Homo sapiens 33-42 20005574-10 2010 The roles of alpha-syn and its interaction with Fe(III) and/or Fe(II) are discussed in the context of oxidative stress, metal-catalyzed alpha-syn aggregation, and iron transfer processes. Iron 163-167 synuclein alpha Homo sapiens 13-22 19166904-0 2009 Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases. Iron 76-80 synuclein alpha Homo sapiens 30-45 18823621-3 2008 Redox active metal ions such as iron (Fe) and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. Iron 32-36 synuclein alpha Homo sapiens 79-94 18823621-3 2008 Redox active metal ions such as iron (Fe) and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. Iron 38-40 synuclein alpha Homo sapiens 79-94 20502498-2 2010 The main component of LB is aggregated alpha-synuclein, present in the substantia nigra where iron accumulation also occurs. Iron 94-98 synuclein alpha Homo sapiens 39-54 20502498-3 2010 The present study aimed to study the relationship between iron and alpha-synuclein aggregation. Iron 58-62 synuclein alpha Homo sapiens 67-82 20502498-7 2010 At the concentrations of 5 mmol/L and 10 mmol/L, iron induced alpha-synuclein aggregation more severely than at the concentration of 1 mmol/L. Iron 49-53 synuclein alpha Homo sapiens 62-77 20141569-3 2010 Alpha-synuclein has also been shown to bind metals including copper and iron. Iron 72-76 synuclein alpha Homo sapiens 0-15 20144654-7 2010 We report that a defective glutathione system and/or inhibited cellular iron efflux have the neurotoxic capacities to initiate a system characteristic of PD; furthermore, these capacities are greatly enhanced with mutated alpha-synuclein proteins. Iron 72-76 synuclein alpha Homo sapiens 222-237 19914207-3 2010 We recently characterized iron-dependent toxic alpha-syn oligomer species by confocal single molecule fluorescence techniques and used this aggregation model to identify several N"-benzylidene-benzohydrazide (NBB) derivatives inhibiting oligomer formation in vitro. Iron 26-30 synuclein alpha Homo sapiens 47-56 19914207-5 2010 Similar to our previous findings in vitro, we found a converse modulation of toxic alpha-syn oligomers by NBB derivates and ferric iron, which was characterized by an increase in aggregate formation by iron and an inhibitory effect of certain NBB compounds. Iron 131-135 synuclein alpha Homo sapiens 83-92 19325037-4 2009 Initially, we showed that only aggregated alpha-synuclein is neurotoxic and requires the presence copper but not iron. Iron 113-117 synuclein alpha Homo sapiens 42-57 19399246-0 2009 Physiological and pathological role of alpha-synuclein in Parkinson"s disease through iron mediated oxidative stress; the role of a putative iron-responsive element. Iron 86-90 synuclein alpha Homo sapiens 39-54 19399246-3 2009 Dysfunction of alpha-synuclein (alpha-syn) has been associated with PD due to its increased presence, together with iron, in Lewy bodies. Iron 116-120 synuclein alpha Homo sapiens 15-30 19399246-3 2009 Dysfunction of alpha-synuclein (alpha-syn) has been associated with PD due to its increased presence, together with iron, in Lewy bodies. Iron 116-120 synuclein alpha Homo sapiens 15-24 19399246-4 2009 Brain oxidative damage caused by iron may be partly mediated by alpha-syn oligomerization during PD pathology. Iron 33-37 synuclein alpha Homo sapiens 64-73 19399246-5 2009 Also, alpha-syn gene dosage can cause familial PD and inhibition of its gene expression by blocking translation via a newly identified Iron Responsive Element-like RNA sequence in its 5"-untranslated region may provide a new PD drug target. Iron 135-139 synuclein alpha Homo sapiens 6-15 18491043-3 2008 Redox-active metal ions such as iron (Fe) and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. Iron 32-36 synuclein alpha Homo sapiens 79-94 18491043-3 2008 Redox-active metal ions such as iron (Fe) and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. Iron 38-40 synuclein alpha Homo sapiens 79-94 18491043-4 2008 In the present investigation, we analyzed the binding efficiency of Cu and Fe to alpha-synuclein by fluorescence studies. Iron 75-77 synuclein alpha Homo sapiens 81-96 18491043-5 2008 It is interesting to note that Cu and Fe showed differential binding pattern toward alpha-synuclein (wild type and A30P, A53T, and E46K mutant forms) as revealed by intrinsic tyrosine fluorescence, thioflavin-T fluorescence, 1-anilino-8-naphthalenesulfonate-binding studies, and scatchard plot analysis. Iron 38-40 synuclein alpha Homo sapiens 84-99 18585086-4 2008 Available data also suggest that the iron released from NM affects the ubiquitin-proteasome system in mitochondria, leading to the failure to clear proteins such as alpha-synuclein and to the development of abnormal alpha-synuclein-immunopositive Lewy bodies that contribute to dopaminergic nerve cell death in PD. Iron 37-41 synuclein alpha Homo sapiens 165-180 18258594-0 2008 Single particle characterization of iron-induced pore-forming alpha-synuclein oligomers. Iron 36-40 synuclein alpha Homo sapiens 62-77 18585086-4 2008 Available data also suggest that the iron released from NM affects the ubiquitin-proteasome system in mitochondria, leading to the failure to clear proteins such as alpha-synuclein and to the development of abnormal alpha-synuclein-immunopositive Lewy bodies that contribute to dopaminergic nerve cell death in PD. Iron 37-41 synuclein alpha Homo sapiens 216-231 17714865-0 2007 Copper- and iron-induced differential fibril formation in alpha-synuclein: TEM study. Iron 12-16 synuclein alpha Homo sapiens 58-73 17531952-3 2007 In the present study, we investigated the stoichiometry of binding of copper [Cu (II)] and iron [Fe (III)] with alpha-synuclein (wild recombinant type and A30P, A53T, E46K mutant forms) using isothermal titration calorimetry (ITC). Iron 91-95 synuclein alpha Homo sapiens 112-127 17325711-0 2007 The 5"-untranslated region of Parkinson"s disease alpha-synuclein messengerRNA contains a predicted iron responsive element. Iron 100-104 synuclein alpha Homo sapiens 50-65 16470637-4 2006 The observations that iron induces aggregation of inert alpha-synuclein and beta-amyloid peptides to toxic aggregates have reinforced the critical role of iron in OS-induced pathogenesis of neurodegeneration, supporting the notion that a combination of iron chelation and antioxidant therapy may be one significant approach for neuroprotection. Iron 22-26 synuclein alpha Homo sapiens 56-71 17296847-9 2007 These observations raise the possibility that these cases of atypical neurodegeneration with brain iron accumulation represent a distinct clinicopathological syndrome and suggest a molecular link between iron deposition and alpha-synuclein accumulation. Iron 99-103 synuclein alpha Homo sapiens 224-239 17296847-9 2007 These observations raise the possibility that these cases of atypical neurodegeneration with brain iron accumulation represent a distinct clinicopathological syndrome and suggest a molecular link between iron deposition and alpha-synuclein accumulation. Iron 204-208 synuclein alpha Homo sapiens 224-239 16000336-10 2005 The increase in pigment density is consistent with previously reported increases associated with oxidation and iron loading, reactions known to precipitate alpha-synuclein. Iron 111-115 synuclein alpha Homo sapiens 156-171 17447435-3 2006 Metal chelation has the potential to prevent iron-induced oxidative stress and aggregation of alpha-synuclein and beta-amyloid peptides. Iron 45-49 synuclein alpha Homo sapiens 94-109 15196967-4 2004 The iron-induced alpha-syn-positive inclusions co-localized largely with ubiquitin, and some of them were positive for nitrotyrosine, lipid, gamma-tubulin and dynein. Iron 4-8 synuclein alpha Homo sapiens 17-26 14742448-0 2004 Alpha-synuclein up-regulation and aggregation during MPP+-induced apoptosis in neuroblastoma cells: intermediacy of transferrin receptor iron and hydrogen peroxide. Iron 137-141 synuclein alpha Homo sapiens 0-15 15231240-5 2004 Iron has also been recently been implicated in promotion of alpha-synuclein aggregation either directly or via increasing levels of oxidative stress suggesting an important role for it in Lewy body formation, another important hallmark of the disease. Iron 0-4 synuclein alpha Homo sapiens 60-75 14742448-3 2004 We investigated the role of transferrin receptor (TfR) and iron in modulating the expression of alpha-synuclein (alpha-syn) in MPP(+)-induced oxidative stress and apoptosis. Iron 59-63 synuclein alpha Homo sapiens 96-111 14742448-3 2004 We investigated the role of transferrin receptor (TfR) and iron in modulating the expression of alpha-synuclein (alpha-syn) in MPP(+)-induced oxidative stress and apoptosis. Iron 59-63 synuclein alpha Homo sapiens 96-105 14742448-8 2004 We conclude that MPP(+)-induced iron signaling is responsible for intracellular oxidant generation, alpha-syn expression, proteasomal dysfunction, and apoptosis. Iron 32-36 synuclein alpha Homo sapiens 100-109 11850416-0 2002 Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. Iron 35-39 synuclein alpha Homo sapiens 63-78 14502650-8 2003 (3) In neurodegeneration with brain iron accumulation type I, or Hallervorden-Spatz disease, alpha-synuclein is present in axonal spheroids and glial and neuronal inclusions. Iron 36-40 synuclein alpha Homo sapiens 93-108 12196137-9 2002 Toxicity induced by alpha-synuclein, NAC and NAC(1-18) oligomers occurs via an apoptotic mechanism, possibly initiated by oxidative damage, since these peptides liberate hydroxyl radicals in the presence of iron. Iron 207-211 synuclein alpha Homo sapiens 20-35 12196137-9 2002 Toxicity induced by alpha-synuclein, NAC and NAC(1-18) oligomers occurs via an apoptotic mechanism, possibly initiated by oxidative damage, since these peptides liberate hydroxyl radicals in the presence of iron. Iron 207-211 synuclein alpha Homo sapiens 37-40 11850416-4 2002 To understand how changes in iron and magnesium might affect the pathophysiology of Parkinson"s disease, we investigated binding of iron to alpha-synuclein, which accumulates in Lewy bodies. Iron 132-136 synuclein alpha Homo sapiens 140-155 11850416-5 2002 Using fluorescence of the four tyrosines in alpha-synuclein as indicators of metal-related conformational changes in alpha-synuclein, we show that iron and magnesium both interact with alpha-synuclein. Iron 147-151 synuclein alpha Homo sapiens 44-59 11850416-5 2002 Using fluorescence of the four tyrosines in alpha-synuclein as indicators of metal-related conformational changes in alpha-synuclein, we show that iron and magnesium both interact with alpha-synuclein. Iron 147-151 synuclein alpha Homo sapiens 117-132 11850416-5 2002 Using fluorescence of the four tyrosines in alpha-synuclein as indicators of metal-related conformational changes in alpha-synuclein, we show that iron and magnesium both interact with alpha-synuclein. Iron 147-151 synuclein alpha Homo sapiens 117-132 11850416-7 2002 Iron lowers both fluorescence peaks, while magnesium increases the fluorescence peak only at 375 nm, which suggests that magnesium affects the conformation of alpha-synuclein differently than iron. Iron 0-4 synuclein alpha Homo sapiens 159-174 11850416-9 2002 In each of these studies, iron increases alpha-synuclein aggregation, while magnesium at concentrations >0.75 mm inhibits the aggregation of alpha-synuclein induced either spontaneously or by incubation with iron. Iron 26-30 synuclein alpha Homo sapiens 41-56 11850416-9 2002 In each of these studies, iron increases alpha-synuclein aggregation, while magnesium at concentrations >0.75 mm inhibits the aggregation of alpha-synuclein induced either spontaneously or by incubation with iron. Iron 211-215 synuclein alpha Homo sapiens 144-159 11850416-10 2002 These data suggest that the conformation of alpha-synuclein can be modulated by metals, with iron promoting aggregation and magnesium inhibiting aggregation. Iron 93-97 synuclein alpha Homo sapiens 44-59 11733371-4 2001 Distinct alpha-SYN species were detected in the detergent-insoluble fractions from brains of patients with PD, dementia with LBs, and neurodegeneration with brain iron accumulation type 1 (formerly known as Hallervorden-Spatz disease). Iron 163-167 synuclein alpha Homo sapiens 9-18 11843096-4 2002 Recent studies suggest that an additional mechanism by which iron might contribute to PD is by inducing aggregation of the alpha-synuclein, which is a protein that accumulates in Lewy bodies in PD. Iron 61-65 synuclein alpha Homo sapiens 123-138 12401952-4 2002 Morphological studies revealed that iron (50-100 microM) altered mitochondrial morphology, disrupted nuclear membrane, and translocated alpha-synuclein from perinuclear region into the disrupted nucleus. Iron 36-40 synuclein alpha Homo sapiens 136-151 10878583-5 2000 Further, alpha-syn was implicated in the formation of the glial (GCIs) and neuronal cytoplasmic inclusions of multiple system atrophy, and the LBs, GCIs and neuraxonal spheroids of neurodegeneration with brain iron accumulation type 1. Iron 210-214 synuclein alpha Homo sapiens 9-18 11724918-8 2001 The presence of alpha-synuclein in GCIs provides a link with Parkinson"s disease, dementia with Lewy bodies, and neurodegeneration with brain iron accumulation, type 1 (or Hallervorden-Spatz syndrome), in which alpha-synuclein is also found within Lewy bodies. Iron 142-146 synuclein alpha Homo sapiens 16-31 11045680-0 2000 Alpha-synuclein accumulation in a case of neurodegeneration with brain iron accumulation type 1 (NBIA-1, formerly Hallervorden-Spatz syndrome) with widespread cortical and brainstem-type Lewy bodies. Iron 71-75 synuclein alpha Homo sapiens 0-15 11677250-2 2001 Recent transcranial ultrasound findings and the observation of the ability of iron to induce aggregation and toxicity of alpha-synuclein have reinforced the critical role of iron in the pathogenesis of nigrostriatal injury. Iron 78-82 synuclein alpha Homo sapiens 121-136 11677250-2 2001 Recent transcranial ultrasound findings and the observation of the ability of iron to induce aggregation and toxicity of alpha-synuclein have reinforced the critical role of iron in the pathogenesis of nigrostriatal injury. Iron 174-178 synuclein alpha Homo sapiens 121-136 11677250-5 2001 Moreover we outline that the interaction of iron with other molecules, especially alpha-synuclein, may contribute to the process of neurodegeneration. Iron 44-48 synuclein alpha Homo sapiens 82-97 10934254-0 2000 The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. Iron 44-48 synuclein alpha Homo sapiens 9-24 10934254-4 2000 Using human BE-M17 neuroblastoma cells overexpressing wild-type, A53T, or A30P alpha-synuclein, we now show that iron and free radical generators, such as dopamine or hydrogen peroxide, stimulate the production of intracellular aggregates that contain alpha-synuclein and ubiquitin. Iron 113-117 synuclein alpha Homo sapiens 79-94 10934254-4 2000 Using human BE-M17 neuroblastoma cells overexpressing wild-type, A53T, or A30P alpha-synuclein, we now show that iron and free radical generators, such as dopamine or hydrogen peroxide, stimulate the production of intracellular aggregates that contain alpha-synuclein and ubiquitin. Iron 113-117 synuclein alpha Homo sapiens 252-267 10934254-8 2000 BE-M17 neuroblastoma cells overexpressing alpha-synuclein show up to a fourfold increase in vulnerability to toxicity induced by iron. Iron 129-133 synuclein alpha Homo sapiens 42-57 10934254-10 2000 These data raise the possibility that alpha-synuclein acts in concert with iron and dopamine to induce formation of Lewy body pathology in PD and cell death in PD. Iron 75-79 synuclein alpha Homo sapiens 38-53 10506125-6 1999 Hemin/hydrogen peroxide similarly induced aggregation of alpha-synuclein, and both cytochrome c/hydrogen peroxide- and hemin/hydrogen peroxide-induced aggregation of alpha-synuclein was partially inhibited by treatment with iron chelator deferoxisamine. Iron 224-228 synuclein alpha Homo sapiens 57-72 10506125-6 1999 Hemin/hydrogen peroxide similarly induced aggregation of alpha-synuclein, and both cytochrome c/hydrogen peroxide- and hemin/hydrogen peroxide-induced aggregation of alpha-synuclein was partially inhibited by treatment with iron chelator deferoxisamine. Iron 224-228 synuclein alpha Homo sapiens 166-181 10506125-7 1999 This indicates that iron-catalyzed oxidative reaction mediated by cytochrome c/hydrogen peroxide might be critically involved in promoting alpha-synuclein aggregation. Iron 20-24 synuclein alpha Homo sapiens 139-154 34083630-7 2021 We also detected significant iron deposition in the injury site, a known catalyst for alpha-synuclein aggregation. Iron 29-33 synuclein alpha Homo sapiens 86-101 10208537-4 1999 Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Iron 114-124 synuclein alpha Homo sapiens 38-42 10208537-4 1999 Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Iron 114-124 synuclein alpha Homo sapiens 43-58 10208537-4 1999 Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Iron 150-154 synuclein alpha Homo sapiens 38-42 10208537-4 1999 Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Iron 150-154 synuclein alpha Homo sapiens 43-58 9748051-0 1998 Lewy body in neurodegeneration with brain iron accumulation type 1 is immunoreactive for alpha-synuclein. Iron 42-46 synuclein alpha Homo sapiens 89-104 9748051-3 1998 Lewy bodies in neurodegeneration with brain iron accumulation type 1 (NBIA 1; Hallervorden-Spatz syndrome) were found to show immunostaining for alpha-synuclein/precursor of non-A beta component of Alzheimer"s disease amyloid, indicating that alpha-synuclein is commonly associated with the formation of Lewy bodies in other sporadic and familial neurodegenerative diseases apart from PD. Iron 44-48 synuclein alpha Homo sapiens 145-160 9748051-3 1998 Lewy bodies in neurodegeneration with brain iron accumulation type 1 (NBIA 1; Hallervorden-Spatz syndrome) were found to show immunostaining for alpha-synuclein/precursor of non-A beta component of Alzheimer"s disease amyloid, indicating that alpha-synuclein is commonly associated with the formation of Lewy bodies in other sporadic and familial neurodegenerative diseases apart from PD. Iron 44-48 synuclein alpha Homo sapiens 243-258 33799121-9 2021 Of note, an atypical IRE exists in the alpha-synuclein 5 UTR that may explain its up-regulation by increased iron. Iron 110-114 synuclein alpha Homo sapiens 39-54 34959389-13 2021 The mRNAs encoding HTT, APP and alphaSYN contain an atypical iron response element (IRE) in their 5"-untranslated regions (5"-UTRs) that bind iron regulatory protein 1 (IRP1), and Posiphen specifically bound this complex. Iron 61-65 synuclein alpha Homo sapiens 32-40 34366375-3 2021 Copper or iron chelators, that bind excess or labile metal ions, can prevent aggregation of alpha-synuclein in the brain and alleviate motor-symptoms in preclinical models of PD. Iron 10-14 synuclein alpha Homo sapiens 92-107 35054862-6 2022 The duo, namely, Fe and Cu, following their inordinate exposure, are viable of permeating across the blood-brain barrier (BBB) and moving inside the brain, thereby culminating in the escalated OS (through a reactive oxygen species (ROS)-reliant pathway), alpha-synuclein aggregation within the LBs, and lipid peroxidation, which consequently results in the destruction of DArgic nerve cells and facilitates PD emanation. Iron 17-19 synuclein alpha Homo sapiens 255-270 35216492-0 2022 Ferritinophagy and alpha-Synuclein: Pharmacological Targeting of Autophagy to Restore Iron Regulation in Parkinson"s Disease. Iron 86-90 synuclein alpha Homo sapiens 19-34 35216492-3 2022 A triad contribution of alpha-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Iron 151-155 synuclein alpha Homo sapiens 24-39 35216492-7 2022 The scope of this review is to describe the physiological and pathological relationship between iron regulation and alpha-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. Iron 96-100 synuclein alpha Homo sapiens 116-131 35172141-0 2022 Interleukin-6 triggers toxic neuronal iron sequestration in response to pathological alpha-synuclein. Iron 38-42 synuclein alpha Homo sapiens 85-100 35417944-3 2022 RESULTS: In the substantia nigra of PD patients, in comparison with the control, a stable accumulation of pathological alpha-synuclein (alpha-Syn-p129) in the bodies and processes of neurons was found, and in the neuroglia and neuropil - the accumulation of iron (II) and ferritin heavy chain, the reaction of microglia to protein CD68 was moderately elevated. Iron 258-262 synuclein alpha Homo sapiens 119-134