PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 22002427-1 2011 Proteolytic cleavage of tau at glutamic acid 391 (E391) is linked to the pathogenesis of Alzheimer disease (AD). Glutamic Acid 31-44 microtubule associated protein tau Homo sapiens 24-27 19642195-1 2010 The microtubule-associated protein tau has been implicated in beta-amyloid- and glutamate-induced neurotoxicity. Glutamic Acid 80-89 microtubule associated protein tau Homo sapiens 4-38 21910444-2 2011 To obtain insight into the structural consequences of phosphorylation, we characterized a mutant protein of tau in which epitopes recognized by Alzheimer diagnostic antibodies were mimicked by mutation to glutamic acid [AT8 (S199E, S202E, T205E), AT100 (T212E and S214E), and PHF1 (S396E and S404E)]. Glutamic Acid 205-218 microtubule associated protein tau Homo sapiens 108-111 18467332-7 2008 Tau mutants with serines and threonines replaced by glutamate, to mimic phosphorylation, showed reduced SH3 binding. Glutamic Acid 52-61 microtubule associated protein tau Homo sapiens 0-3 18725412-6 2008 To avoid the ambiguities of heterogeneous phosphorylation we cloned "pseudo-phosphorylation" mutants of Tau where combinations of Ser or Thr residues were converted into Glu. Glutamic Acid 170-173 microtubule associated protein tau Homo sapiens 104-107 16407562-0 2006 Impaired glutamate transport in a mouse model of tau pathology in astrocytes. Glutamic Acid 9-18 microtubule associated protein tau Homo sapiens 49-52 10961425-6 2000 Glutamate induces an enhancement of tau gene expression in resistant neurons whereas a reduced expression is noted in apoptotic cells. Glutamic Acid 0-9 microtubule associated protein tau Homo sapiens 36-39 14627651-5 2003 These results suggest that reduced stable Glu-MTs is a primary consequence of tau accumulation that initiates mechanisms underlying astrocyte dysfunction and death in human neurodegenerative glial tauopathies. Glutamic Acid 42-45 microtubule associated protein tau Homo sapiens 78-81 12769185-3 2003 In the hippocampal slice model, tau deposits and amyloidogenic fragments induced by the lysosomal inhibitor chloroquine were accompanied by disrupted microtubule integrity and by corresponding declines in postsynaptic glutamate receptors and the presynaptic marker synaptophysin. Glutamic Acid 218-227 microtubule associated protein tau Homo sapiens 32-35 3099793-2 1986 Tau polymerization requires of a previous modification; conversion of glutamine into glutamic acid by deamination. Glutamic Acid 85-98 microtubule associated protein tau Homo sapiens 0-3 10461542-11 1999 MAM alters gene expression in SY5Y human neuroblastoma cells and, in the presence of DNA damage and reduced DNA repair, enhances glutamate-modulated expression of tau mRNA in rat primary neurons; the corresponding protein (TAU) is elevated in ALS/PDC and Alzheimer"s disease. Glutamic Acid 129-138 microtubule associated protein tau Homo sapiens 163-166 10461542-11 1999 MAM alters gene expression in SY5Y human neuroblastoma cells and, in the presence of DNA damage and reduced DNA repair, enhances glutamate-modulated expression of tau mRNA in rat primary neurons; the corresponding protein (TAU) is elevated in ALS/PDC and Alzheimer"s disease. Glutamic Acid 129-138 microtubule associated protein tau Homo sapiens 223-226 10461544-4 1999 In cultures exposed to mild glutamate toxicity, tau mRNA expression, not beta-actin, is enhanced in stressed neurons. Glutamic Acid 28-37 microtubule associated protein tau Homo sapiens 48-51 10461544-5 1999 The Guam cycad toxin metabolite methylazoxymethanol also produces an increase of tau gene transcription that exacerbates changes induced by glutamate. Glutamic Acid 140-149 microtubule associated protein tau Homo sapiens 81-84 10461544-6 1999 In serum-deprived cultures or glutamate-exposed cultures, neurons committed to apoptosis have a reduced tau gene expression, whereas resistant neurons display a stable or even augmented tau mRNA expression accompanied by a persistent tau phosphorylation near serine 202. Glutamic Acid 30-39 microtubule associated protein tau Homo sapiens 104-107 10461544-6 1999 In serum-deprived cultures or glutamate-exposed cultures, neurons committed to apoptosis have a reduced tau gene expression, whereas resistant neurons display a stable or even augmented tau mRNA expression accompanied by a persistent tau phosphorylation near serine 202. Glutamic Acid 30-39 microtubule associated protein tau Homo sapiens 186-189 10461544-6 1999 In serum-deprived cultures or glutamate-exposed cultures, neurons committed to apoptosis have a reduced tau gene expression, whereas resistant neurons display a stable or even augmented tau mRNA expression accompanied by a persistent tau phosphorylation near serine 202. Glutamic Acid 30-39 microtubule associated protein tau Homo sapiens 186-189 9427355-2 1997 It recognizes tau molecules which are cleaved at Glu-391, suggesting that tau is endogenously truncated in AD brains. Glutamic Acid 49-52 microtubule associated protein tau Homo sapiens 14-17 9427355-2 1997 It recognizes tau molecules which are cleaved at Glu-391, suggesting that tau is endogenously truncated in AD brains. Glutamic Acid 49-52 microtubule associated protein tau Homo sapiens 74-77 8781663-1 1996 Tau protein, which is incorporated into the core of paired helical filaments (PHFs) in Alzheimer"s disease (AD), can be characterised immunochemically by C-terminal truncation at Glu-391 recognised by monoclonal antibody (mAb) 423, and acid-reversible occlusion of a generic tau epitope in the tandem repeat region recognised by mAb 7.51. Glutamic Acid 179-182 microtubule associated protein tau Homo sapiens 0-3 8781663-4 1996 We report that the early abnormal tau deposits in cells vulnerable to neurofibrillary degeneration are characterised by C-terminal truncation at Glu-391, acid-reversible occlusion of the mAb 7.51 epitope, and the absence of binding sites for thiazin red, consistent with the amorphous non-fibrillar structure demonstrated by immunoelectron microscopy. Glutamic Acid 145-148 microtubule associated protein tau Homo sapiens 34-37 1351785-0 1992 A dose-dependent increase of Tau immunostaining is produced by glutamate toxicity in primary neuronal cultures. Glutamic Acid 63-72 microtubule associated protein tau Homo sapiens 29-32 1351785-7 1992 Our findings indicate that glutamate induces a dose-dependent increase of Tau immunoreactivity directly related to its cellular action on neuronal cells. Glutamic Acid 27-36 microtubule associated protein tau Homo sapiens 74-77 34591222-4 2022 This review focuses on evidence in the literature that describes how one potential age-related change, that of glutamate-mediated increases in neuronal activity, may ultimately increase the risk of developing AD and promote the spread of tau pathology in AD-affected brains from the EC to later regions such as the hippocampus and prefrontal cortex. Glutamic Acid 111-120 microtubule associated protein tau Homo sapiens 238-241 34786841-4 2021 Downstream events including, phagocytosis of synapses and persistent glutamate signaling through N-methyl-D-aspartate receptors drive neurodegeneration and tau pathology. Glutamic Acid 69-78 microtubule associated protein tau Homo sapiens 156-159 34769068-6 2021 These behavioral changes may be due to enhanced late-stage tau pathology, as evidenced by immunoblotting and exacerbated hippocampal dysregulation of glutamate release and uptake measured by the microelectrode array technique. Glutamic Acid 150-159 microtubule associated protein tau Homo sapiens 59-62 34469725-4 2021 We also find that elevated glutamate release probability is required for Abetao-induced pathological hyperphosphorylation of tau, which is likewise NMDAR dependent. Glutamic Acid 27-36 microtubule associated protein tau Homo sapiens 125-128 34469725-6 2021 Together, these results support a possible causal chain in which Abetao increases glutamate release probability, thus leading to enhanced LTD induction, which in turn drives hyperphosphorylation of tau. Glutamic Acid 82-91 microtubule associated protein tau Homo sapiens 198-201 34416145-3 2021 (2021) report cerebral organoids that reveal early events in frontotemporal dementia pathogenesis due to mutations in microtubule-associated protein tau (MAPT), shedding light on a novel mechanism involving abnormal splicing and glutamate signaling. Glutamic Acid 229-238 microtubule associated protein tau Homo sapiens 118-152 34416145-3 2021 (2021) report cerebral organoids that reveal early events in frontotemporal dementia pathogenesis due to mutations in microtubule-associated protein tau (MAPT), shedding light on a novel mechanism involving abnormal splicing and glutamate signaling. Glutamic Acid 229-238 microtubule associated protein tau Homo sapiens 154-158 35038671-4 2022 An increase in posterior cingulate gyrus tau deposition, but not elevated Abeta, was associated with lower N-acetylaspartate/total creatine (tCr) and glutamate (Glu)/tCr ratios, and sex by tau interaction was observed in association with Glu/tCr. Glutamic Acid 150-159 microtubule associated protein tau Homo sapiens 41-44 35038671-4 2022 An increase in posterior cingulate gyrus tau deposition, but not elevated Abeta, was associated with lower N-acetylaspartate/total creatine (tCr) and glutamate (Glu)/tCr ratios, and sex by tau interaction was observed in association with Glu/tCr. Glutamic Acid 161-164 microtubule associated protein tau Homo sapiens 41-44 35038671-4 2022 An increase in posterior cingulate gyrus tau deposition, but not elevated Abeta, was associated with lower N-acetylaspartate/total creatine (tCr) and glutamate (Glu)/tCr ratios, and sex by tau interaction was observed in association with Glu/tCr. Glutamic Acid 238-241 microtubule associated protein tau Homo sapiens 41-44 35358667-0 2022 Dendritic distribution of CDK5 mRNA and p35 mRNA, and a glutamate-responsive increase of CDK5/p25 complex contribute to tau hyperphosphorylation. Glutamic Acid 56-65 microtubule associated protein tau Homo sapiens 120-123 35274343-0 2022 Extracellular tau oligomers affect extracellular glutamate handling by astrocytes through downregulation of GLT-1 expression and impairment of NKA1A2 function. Glutamic Acid 49-58 microtubule associated protein tau Homo sapiens 14-17 35274343-3 2022 We previously demonstrated that extracellular tau oligomers (ex-oTau), by specifically targeting astrocytes, affect glutamate-dependent synaptic transmission via a reduction in gliotransmitter release. Glutamic Acid 116-125 microtubule associated protein tau Homo sapiens 46-49 33616735-6 2021 Remarkably, serum glutamate levels were significantly higher in patients affected by early AD phases compared to controls, and were negatively correlated with CSF total tau levels. Glutamic Acid 18-27 microtubule associated protein tau Homo sapiens 169-172 33303219-5 2021 The model comprises 8 variants from 4 previously identified (BIN1, PTK2B, PICALM, APOE) and 2 novel (DLG2, MINK1) LOAD loci involved in glutamate signaling (p = 0.01) or APP catabolism or tau binding (p = 0.005). Glutamic Acid 136-145 microtubule associated protein tau Homo sapiens 188-191 27721502-6 2016 Chemogenetic or pharmacological control of neuronal activity-relevant Ca2+ influx by the introduction of designer receptors exclusively activated by designer drugs (DREADDs) or by the treatment with glutamate receptor blockers attenuated misfolded tau accumulation and neuronal death. Glutamic Acid 199-208 microtubule associated protein tau Homo sapiens 248-251 33246331-7 2021 Unexpectedly, phosphorylated tau was primarily accumulated in glutamic acid decarboxylase 67 (GAD67) GABAergic interneurons and, to a lesser extent, glutamate receptor 2/3-positive excitatory mossy cells, showing preferential extracellular vesicle-mediated GABAergic interneuronal tau propagation. Glutamic Acid 62-75 microtubule associated protein tau Homo sapiens 29-32 33075193-3 2021 This postulate rests on extensive data demonstrating that in human brains tau pathology appears about a decade before the formation of Abeta plaques (Abetaps), especially targeting glutamate projection neurons in the association cortex. Glutamic Acid 181-190 microtubule associated protein tau Homo sapiens 74-77 31904014-3 2019 We have recently demonstrated that nuclear Tau is involved in the expression of the VGluT1 gene, suggesting a molecular mechanism that could explain the pathological increase of glutamate release in the early stages of Alzheimer"s disease. Glutamic Acid 178-187 microtubule associated protein tau Homo sapiens 43-46 30251689-4 2018 Glutamate (125 muM) produced hyperphosphorylation of tau in cortical primary cultures along with increased apoptotic nuclei, LDH release, and cPLA2 expression, which were all reversed by BACE1-KD. Glutamic Acid 0-9 microtubule associated protein tau Homo sapiens 53-56 31774919-5 2019 This includes tau-dependent neurodegeneration, where astrocytes lose key molecules involved in regulation of glutamate/glutamine homeostasis, neuronal survival and synaptogenesis. Glutamic Acid 109-118 microtubule associated protein tau Homo sapiens 14-17 32096031-5 2019 In organotypic slices these abnormal states can be reversed by drugs, e.g. Tau aggregation inhibitors or modulators of glutamate uptake. Glutamic Acid 119-128 microtubule associated protein tau Homo sapiens 75-78 26070304-6 2015 At low doses, Poly-APS was non-toxic and cultured cells exposed to Poly-APS (0.5 microg/ml) and hTau (1 microg/ml; ~22 microM) had normal input resistance, resting-state membrane potentials and Ca(2+) transients induced either by glutamate or KCl, as did cells exposed to a low concentration of the phosphatase inhibitor Okadaic acid (OA; 1 nM, 24 h). Glutamic Acid 230-239 microtubule associated protein tau Homo sapiens 96-100 26971324-5 2016 This review discusses that both beta-amyloid (Abeta) and tau perturb synaptic functioning of the tripartite synapse, including alterations in glutamate release, astrocytic uptake, and receptor signaling. Glutamic Acid 142-151 microtubule associated protein tau Homo sapiens 57-60 26931569-8 2016 In summary, hTau(AT) causes excitotoxicity mediated by NR2B-containing NMDA receptors due to enhanced extracellular glutamate. Glutamic Acid 116-125 microtubule associated protein tau Homo sapiens 12-16 26070304-7 2015 Combined hTau loading and phosphatase inhibition resulted in a collapse of the membrane potential, suppressed excitation and diminished glutamate and KCl-stimulated Ca(2+) transients. Glutamic Acid 136-145 microtubule associated protein tau Homo sapiens 9-13 24534188-6 2014 Importantly, presynaptic glutamate release is sufficient to drive tau release. Glutamic Acid 25-34 microtubule associated protein tau Homo sapiens 66-69 22334661-2 2012 To explore this possibility, we treated cultured hippocampal slices or primary neurons with glutamate or Bic/4-AP to increase the synaptic activity with or without pretreatment of zinc chelators, and then detected the phosphorylation levels of tau. Glutamic Acid 92-101 microtubule associated protein tau Homo sapiens 244-247 22334661-3 2012 We found that glutamate or Bic/4-AP treatment caused tau hyperphosphorylation at multiple AD-related sites, including Ser-396, Ser-404, Thr-231, and Thr-205, while application of intracellular or extracellular zinc chelators, or blockade of zinc release by extracellular calcium omission almost abolished the synaptic activity-associated tau hyperphosphorylation. Glutamic Acid 14-23 microtubule associated protein tau Homo sapiens 338-341 22334661-3 2012 We found that glutamate or Bic/4-AP treatment caused tau hyperphosphorylation at multiple AD-related sites, including Ser-396, Ser-404, Thr-231, and Thr-205, while application of intracellular or extracellular zinc chelators, or blockade of zinc release by extracellular calcium omission almost abolished the synaptic activity-associated tau hyperphosphorylation. Glutamic Acid 14-23 microtubule associated protein tau Homo sapiens 53-56 21919991-1 2012 Pathological processing of tau protein during the formation and maturation of neurofibrillary tangles (NFTs) includes abnormal phosphorylation, conformational changes and truncation of the C-terminus at aspartic-acid(421) (apoptotic product) and glutamic-acid(391) residues. Glutamic Acid 247-260 microtubule associated protein tau Homo sapiens 27-30