PMID-sentid	Pub_year	Sent_text	comp_official_name	comp_offset	protein_name	organism	prot_offset
32890589-2	2020	The rapamycin derivative ("rapalog") everolimus, which allosterically inhibits the mTOR pathway, is approved for the treatment of partial epilepsy with spontaneous recurrent seizures (SRS) in individuals with tuberous sclerosis complex (TSC).	Sirolimus	4-13	TSC complex subunit 1	Mus musculus	237-240
1732043-19	1992	In cytosolic extracts from parental GC3/C1 (TS+) cells, [6R]CH2-H4PteGlu1 acted as a cofactor in the release of 3H2O from [5-3H]dUMP, whereas no activity was detected in cytosols from TS-C1/C1.	3h2o	112-116	TSC complex subunit 1	Mus musculus	184-189
1732043-19	1992	In cytosolic extracts from parental GC3/C1 (TS+) cells, [6R]CH2-H4PteGlu1 acted as a cofactor in the release of 3H2O from [5-3H]dUMP, whereas no activity was detected in cytosols from TS-C1/C1.	Tritium	112-114	TSC complex subunit 1	Mus musculus	184-189
33767704-4	2021	Here, by using a mouse model of renal ischemia-reperfusion, we found that myeloid cell-specific TSC1 knockout mice (termed Lyz-TSC1 cKO mice) had higher serum creatinine levels, more severe histological damage, and greater proinflammatory cytokine production than wild-type (WT) mice during the early phase after renal ischemia-reperfusion.	Creatinine	159-169	TSC complex subunit 1	Mus musculus	96-100
32890589-2	2020	The rapamycin derivative ("rapalog") everolimus, which allosterically inhibits the mTOR pathway, is approved for the treatment of partial epilepsy with spontaneous recurrent seizures (SRS) in individuals with tuberous sclerosis complex (TSC).	Everolimus	37-47	TSC complex subunit 1	Mus musculus	237-240
32890589-9	2020	The main advantage of the novel 1,3,5-triazine derivatives is their excellent tolerability compared to rapalogs, which would favor their development as new therapies for TORopathies such as TSC.	1,3,5-TRIAZINE	32-46	TSC complex subunit 1	Mus musculus	190-193
32890589-9	2020	The main advantage of the novel 1,3,5-triazine derivatives is their excellent tolerability compared to rapalogs, which would favor their development as new therapies for TORopathies such as TSC.	rapalogs	103-111	TSC complex subunit 1	Mus musculus	190-193
34677125-3	2021	Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Muller glia (MG) that degenerate from senescence-associated cell death.	Sirolimus	64-73	TSC complex subunit 1	Mus musculus	125-153
34365025-4	2021	Herein, we report that constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling via Tsc1 (Tuberous sclerosis 1) deletion in chondrocytes causes abnormal skull development with decreased size and rounded shape.	Sirolimus	76-85	TSC complex subunit 1	Mus musculus	119-123
34365025-4	2021	Herein, we report that constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling via Tsc1 (Tuberous sclerosis 1) deletion in chondrocytes causes abnormal skull development with decreased size and rounded shape.	Sirolimus	76-85	TSC complex subunit 1	Mus musculus	125-145
34677125-3	2021	Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Muller glia (MG) that degenerate from senescence-associated cell death.	Sirolimus	64-73	TSC complex subunit 1	Mus musculus	155-159
34535574-8	2021	Tsc1-deficient mTECs exhibited overproduction of reactive oxygen species and malfunction of lysosome, with lysosome membrane permeabilization and the release of cathepsin B and cathepsin L to the cytosol, which then lead to Bid cleaved into active truncated Bid and subsequently intrinsic apoptosis.	Oxygen	58-64	TSC complex subunit 1	Mus musculus	0-4
35275098-5	2022	After rescuing the phosphorylation of S6 and 4EBP1 by silencing Tsc1, the suppressive effects of PIKfyve inhibition on glucose utilization, proliferation and migration in VSMCs were abolished.	Glucose	119-126	TSC complex subunit 1	Mus musculus	64-68
34380034-0	2021	Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning.	Endocannabinoids	58-73	TSC complex subunit 1	Mus musculus	8-12
34380034-4	2021	We find that dSPN-specific loss of Tsc1 impairs endocannabinoid-mediated long-term depression (eCB-LTD) at cortico-dSPN synapses and strongly enhances corticostriatal synaptic drive, which is not observed in iSPNs.	Endocannabinoids	48-63	TSC complex subunit 1	Mus musculus	35-39
34253722-1	2021	Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1).	Sirolimus	128-137	TSC complex subunit 1	Mus musculus	28-31
34253722-1	2021	Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1).	Sirolimus	128-137	TSC complex subunit 1	Mus musculus	46-50
35400999-10	2022	Moreover, we found that miR-126-3p could inhibit TSC1 expression, which further activated mTORC1 signaling and increased HIF-1alpha and VEGFA expression, ultimately promoting angiogenesis.	mir-126-3p	24-34	TSC complex subunit 1	Mus musculus	49-53
33352197-0	2021	Rapamycin ameliorates corneal injury after alkali burn through methylation modification in mouse TSC1 and mTOR genes.	Sirolimus	0-9	TSC complex subunit 1	Mus musculus	97-101
33957945-8	2021	Moreover, expression of the gamma-amino butyric acid (GABA) receptor in the brains of Tsc1RORgammat mice was decreased, and GABA supplementation prolonged the lifespan of the mice to some extent.	gamma-Aminobutyric Acid	28-52	TSC complex subunit 1	Mus musculus	86-90
33957945-8	2021	Moreover, expression of the gamma-amino butyric acid (GABA) receptor in the brains of Tsc1RORgammat mice was decreased, and GABA supplementation prolonged the lifespan of the mice to some extent.	gamma-Aminobutyric Acid	54-58	TSC complex subunit 1	Mus musculus	86-90
33968030-5	2021	The inhibitory effects on the mTORC1 signaling by metformin was dependent on the tuberous sclerosis complex 1 (TSC1).	Metformin	50-59	TSC complex subunit 1	Mus musculus	81-109
33968030-5	2021	The inhibitory effects on the mTORC1 signaling by metformin was dependent on the tuberous sclerosis complex 1 (TSC1).	Metformin	50-59	TSC complex subunit 1	Mus musculus	111-115
33536341-6	2021	In addition, the electrogenic 2Cl-/H+ exchanger (CLC-5) is significantly up-regulated and shows remarkable colocalization with H+-ATPase on the apical membrane of cyst epithelia in Tsc1 KO mice.	2,6-Dichlorophenylacetic acid	30-33	TSC complex subunit 1	Mus musculus	181-185
35121635-11	2022	These results suggest that the Rheb1 activation may be responsible for synaptic abnormalities and memory impairments in Tsc2+/- mice, and its inhibition by lonafarnib could provide insight into potential treatment options for TSC-associated neuropsychiatric disorders (TANDs).SIGNIFICANCE STATEMENTTuberous sclerosis complex (TSC) is an autosomal dominant disease that causes neuropsychiatric symptoms, including intractable epilepsy, intellectual disability (ID) and autism.	lonafarnib	156-166	TSC complex subunit 1	Mus musculus	326-329
35121635-15	2022	Lonafarnib treatment increased inactive Rheb1, and recovered proper synapse formation and plasticity-related Arc expression in TSC neurons.	lonafarnib	0-10	TSC complex subunit 1	Mus musculus	127-130
35121635-16	2022	Furthermore, in vivo lonafarnib treatment restored contextual memory and Arc induction in TSC mice.	lonafarnib	21-31	TSC complex subunit 1	Mus musculus	90-93
33352197-4	2021	To this end, we used bisulfite sequencing polymerase chain reaction and Western blot analysis, to study the effects of 5-aza-2"-deoxycytidine and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, which inhibit methyltransferase and PI3K respectively, on DNA methylation and expression of downstream effectors of PI3K related to corneal NV, including TSC1 and mTOR genes.	2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	146-194	TSC complex subunit 1	Mus musculus	350-354
32927859-6	2020	In young (28 day old) mice, Tsc1 deficiency-induced significant cell expansion of non-hematopoietic BM in vivo, and MSC colony-forming potential in vitro, that was normalized upon treatment with the mTOR inhibitor, everolimus.	Everolimus	215-225	TSC complex subunit 1	Mus musculus	28-32
33159078-1	2020	Lymphangioleiomyomatosis (LAM) is a rare fatal cystic lung disease due to bi-allelic inactivating mutations in tuberous sclerosis complex (TSC1/TSC2) genes coding for suppressors of the mechanistic target of rapamycin complex 1 (mTORC1).	Sirolimus	208-217	TSC complex subunit 1	Mus musculus	139-143
32738450-13	2021	The mTOR inhibitor rapamycin significantly reduced hepatocarcinogenesis triggered by Tsc1 loss and p53 haploinsufficiency in vivo, as well as the biomarker Abcc4.	Sirolimus	19-28	TSC complex subunit 1	Mus musculus	85-89
32927859-7	2020	The hyperproliferative BM-MSC phenotype was lost in aged (1.5 yr) mice, and Tsc1 inactivation was also accompanied by elevated ROS and increased senescence.	ros	127-130	TSC complex subunit 1	Mus musculus	76-80
32484794-4	2020	Injection of rapamycin to pregnant mice inhibited the mTOR pathway and tubular cell proliferation in kidneys of TSC1 null offspring.	Sirolimus	13-22	TSC complex subunit 1	Mus musculus	112-116
32588887-2	2020	TSC results from inactivating variants within the TSC1 or TSC2 genes, leading to constitutive activation of mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling.	Sirolimus	130-139	TSC complex subunit 1	Mus musculus	0-3
32588887-2	2020	TSC results from inactivating variants within the TSC1 or TSC2 genes, leading to constitutive activation of mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling.	Sirolimus	130-139	TSC complex subunit 1	Mus musculus	50-54
32588887-3	2020	Using a mouse model of TSC (Tsc2-RG) in which the Tsc2 gene is deleted in radial glial precursors and their neuronal and glial descendants, we observed increased ornithine decarboxylase (ODC) enzymatic activity and concentration of its product, putrescine.	Putrescine	245-255	TSC complex subunit 1	Mus musculus	23-26
32484794-6	2020	Gene expression analysis of proximal tubule cells, identified sets of genes and pathways that were modified secondary to TSC1 deletion and rescued by rapamycin administration during nephrogenesis.	Sirolimus	150-159	TSC complex subunit 1	Mus musculus	121-125
32566257-0	2020	Metformin effectively treats Tsc1 deletion-caused kidney pathology by upregulating AMPK phosphorylation.	Metformin	0-9	TSC complex subunit 1	Mus musculus	29-33
32566257-5	2020	We therefore treated Tsc1 ptKO mice with the AMPK activator, metformin, by daily intraperitoneal injection.	Metformin	61-70	TSC complex subunit 1	Mus musculus	21-25
31506280-0	2019	Tumors with TSC mutations are sensitive to CDK7 inhibition through NRF2 and glutathione depletion.	Glutathione	76-87	TSC complex subunit 1	Mus musculus	12-15
32404875-7	2020	Furthermore, haploinsufficiency for Tsc1 in tubular cells led to Rheb1 activation and mitigated cisplatin-induced cell death, mitochondrial defect and AKI.	Cisplatin	96-105	TSC complex subunit 1	Mus musculus	36-40
32375878-2	2020	TSC1 and TSC2 are repressors of the mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of protein synthesis.	Sirolimus	58-67	TSC complex subunit 1	Mus musculus	0-4
31955578-1	2020	Recent clinical evaluation of everolimus for seizure reduction in patients with tuberous sclerosis complex (TSC), a disease with overactivated mechanistic target of rapamycin (mTOR) signaling, has demonstrated the therapeutic value of mTOR inhibitors for central nervous system (CNS) indications.	Everolimus	30-40	TSC complex subunit 1	Mus musculus	108-111
31024074-6	2019	While CM from Tsc1-/- fibroblasts promoted tubular cell c-met signaling activation and inhibited staurosporine-induced cell apoptosis.	Staurosporine	97-110	TSC complex subunit 1	Mus musculus	14-18
32274803-3	2020	Infantile spasms in TSC are particularly characteristic in its strong responsiveness to vigabatrin.	Vigabatrin	88-98	TSC complex subunit 1	Mus musculus	20-23
32274803-11	2020	Tsc1GFAP CKO mice had spontaneous focal seizures in the early neonatal period and a reduced threshold for NMDA-induced spasms, but no spontaneous spasms were observed.	N-Methylaspartate	106-110	TSC complex subunit 1	Mus musculus	0-8
31235817-6	2019	Transfection of the cells with TSC1 mimic significantly ameliorated HG-induced EMT of HK-2 cells.	Mercury	68-70	TSC complex subunit 1	Mus musculus	31-35
31325707-0	2019	5-Aza-2"-deoxycytidine increases hypoxia tolerance-dependent autophagy in mouse neuronal cells by initiating the TSC1/mTOR pathway.	Decitabine	0-22	TSC complex subunit 1	Mus musculus	113-117
30295710-4	2019	Here we report that a stable analogue of diadenosine-tetraphosphate: AppCH2ppA effectively suppresses spontaneous epileptiform activity in vitro and in vivo in a Tuberous Sclerosis Complex (TSC) mouse model (Tsc1+/-), and in postsurgery cortical samples from TSC human patients.	diadenosine tetraphosphate	41-67	TSC complex subunit 1	Mus musculus	190-193
30760873-5	2019	Augmented xCT led to reduction of eumelanin and elevation of pheomelanin in Tsc1 skin knockout mice through mTOR signaling pathway.	pheomelanin	61-72	TSC complex subunit 1	Mus musculus	76-80
31078684-6	2019	Loss of either Tsc1 or Tsc2 from astrocytes resulted in a marked increase in Aqp4 expression which was sensitive to mTORC1 inhibition with rapamycin.	Sirolimus	139-148	TSC complex subunit 1	Mus musculus	15-19
31433805-3	2019	Here, we demonstrate a special metabolic-epigenetic coupling mechanism orchestrated by tuberous sclerosis complex subunit 1 (TSC1)-mechanistic target of rapamycin (mTOR) for homeostatic DC function.	Sirolimus	153-162	TSC complex subunit 1	Mus musculus	87-123
31433805-3	2019	Here, we demonstrate a special metabolic-epigenetic coupling mechanism orchestrated by tuberous sclerosis complex subunit 1 (TSC1)-mechanistic target of rapamycin (mTOR) for homeostatic DC function.	Sirolimus	153-162	TSC complex subunit 1	Mus musculus	125-129
31433805-6	2019	Mechanistically, our data suggest that the steady-state DCs tend to tune down de novo fatty acid synthesis and divert acetyl-coenzyme A (acetyl-CoA) for histone acetylation, a process critically controlled by TSC1-mTOR.	Acetyl Coenzyme A	118-135	TSC complex subunit 1	Mus musculus	209-213
31433805-6	2019	Mechanistically, our data suggest that the steady-state DCs tend to tune down de novo fatty acid synthesis and divert acetyl-coenzyme A (acetyl-CoA) for histone acetylation, a process critically controlled by TSC1-mTOR.	Acetyl Coenzyme A	137-147	TSC complex subunit 1	Mus musculus	209-213
30295710-4	2019	Here we report that a stable analogue of diadenosine-tetraphosphate: AppCH2ppA effectively suppresses spontaneous epileptiform activity in vitro and in vivo in a Tuberous Sclerosis Complex (TSC) mouse model (Tsc1+/-), and in postsurgery cortical samples from TSC human patients.	diadenosine tetraphosphate	41-67	TSC complex subunit 1	Mus musculus	208-212
30295710-4	2019	Here we report that a stable analogue of diadenosine-tetraphosphate: AppCH2ppA effectively suppresses spontaneous epileptiform activity in vitro and in vivo in a Tuberous Sclerosis Complex (TSC) mouse model (Tsc1+/-), and in postsurgery cortical samples from TSC human patients.	diadenosine tetraphosphate	41-67	TSC complex subunit 1	Mus musculus	259-262
30733194-3	2019	Deletion of Tsc1 in mouse embryonic fibroblasts (MEF) decreased phosphorylation of c-MYC at threonine 58 (pT58) and increased phosphorylation at serine 62 (pS62), an observation validated in prostate cancer cells.	Threonine	92-101	TSC complex subunit 1	Mus musculus	12-16
31088907-1	2019	We discovered that 90.3% of patients with angiomyolipomas, lymphangioleiomyomatosis (LAM), and tuberous sclerosis complex (TSC) carry the arginine variant of codon 72 (R72) of TP53 and that R72 increases the risk for angiomyolipoma.	Arginine	138-146	TSC complex subunit 1	Mus musculus	123-126
31353861-8	2019	Tsc1 gene deletion resulted in a strong activation of the mTORC1 pathway, and both epileptogenesis and lethality could be entirely prevented by RHEB1 gene deletion or rapamycin treatment.	Sirolimus	167-176	TSC complex subunit 1	Mus musculus	0-4
30733194-3	2019	Deletion of Tsc1 in mouse embryonic fibroblasts (MEF) decreased phosphorylation of c-MYC at threonine 58 (pT58) and increased phosphorylation at serine 62 (pS62), an observation validated in prostate cancer cells.	Serine	145-151	TSC complex subunit 1	Mus musculus	12-16
30247156-8	2018	Treatment with rapamycin and the antioxidant N-acetylcysteine rescued Tsc1-cKO hair cells from injury in vivo.	Sirolimus	15-24	TSC complex subunit 1	Mus musculus	70-74
30816216-2	2019	Dysregulation of mTOR signaling has been implicated in the pathogenesis of certain types of ASD, and inhibition of mTOR by rapamycin has been demonstrated to be an effective therapeutics for impaired social interaction in Tsc1+/-, Tsc2+/-, Pten-/- mice and valproic acid-induced ASD animal models.	Sirolimus	123-132	TSC complex subunit 1	Mus musculus	222-226
30622053-3	2019	Activation of mTOR complex 1 (mTORC1) causes addiction to glucose and glutamine in Tsc1-/-or Tsc2-/- mouse embryonic fibroblasts (MEFs).	Glucose	58-65	TSC complex subunit 1	Mus musculus	83-87
30622053-3	2019	Activation of mTOR complex 1 (mTORC1) causes addiction to glucose and glutamine in Tsc1-/-or Tsc2-/- mouse embryonic fibroblasts (MEFs).	Glutamine	70-79	TSC complex subunit 1	Mus musculus	83-87
30461191-6	2019	Furthermore, follicular development disorder induced by nano TiO2 was associated with upregulation of TGF-beta1, TGF-betaR1, PTEN, and Foxo3a involved in cell growth and apoptosis and downregulation of several growth factors (PI3K, AKT, p-mTOR, p70S6K, p-p70S6K1, rpS6, p-rpS6, TSC1, and TSC2) in mouse ovaries.	titanium dioxide	61-65	TSC complex subunit 1	Mus musculus	278-282
30247156-8	2018	Treatment with rapamycin and the antioxidant N-acetylcysteine rescued Tsc1-cKO hair cells from injury in vivo.	Acetylcysteine	45-61	TSC complex subunit 1	Mus musculus	70-74
29396625-7	2018	The elongated cilium phenotype of Tsc1-/- MEFs is likely due to increased mTORC1-dependent autophagic flux observed in these cells, as both the autophagic flux and the cilia length phenotype was restored by rapamycin.	Sirolimus	207-216	TSC complex subunit 1	Mus musculus	34-38
30185506-5	2018	Rapamycin, an mTORC1 inhibitor, and bosentan, an EDN1 antagonist, eliminated the difference in renal function between TSC1fl/fl and Fibro-TSC1-/- mice after LPS injection.	Bosentan	36-44	TSC complex subunit 1	Mus musculus	118-122
30185506-5	2018	Rapamycin, an mTORC1 inhibitor, and bosentan, an EDN1 antagonist, eliminated the difference in renal function between TSC1fl/fl and Fibro-TSC1-/- mice after LPS injection.	Bosentan	36-44	TSC complex subunit 1	Mus musculus	138-142
30185506-6	2018	Rapamycin restored LPS-induced up-regulation of EDN1, endothelin converting enzyme-1 (ECE1), and p-JNK in TSC1-knockdown mouse embryonic fibroblasts (MEFs).	Sirolimus	0-9	TSC complex subunit 1	Mus musculus	106-110
30185506-7	2018	SP600125, a Jun-amino-terminal kinase (JNK) inhibitor, attenuated LPS-induced enhancement of EDN1 and ECE1 in TSC1-knockdown MEFs without a change in phospho-S6 ribosomal protein (p-S6) level.	pyrazolanthrone	0-8	TSC complex subunit 1	Mus musculus	110-114
30079598-5	2018	RESULTS: Tsc1Cx3cr1-Cre CKO mice exhibited a high efficiency of microglia Tsc1 inactivation, mTORC1 activation, increased microglial size and number, and robust epilepsy, which were rapamycin-dependent.	Sirolimus	182-191	TSC complex subunit 1	Mus musculus	9-13
30079598-7	2018	In contrast, postnatal inactivation of Tsc1 utilizing a tamoxifen-inducible Cx3cr1-CreER resulted in a more-selective microglia Tsc1 inactivation with high efficiency, mTORC1 activation, and increased microglial size and number, but no documented epilepsy.	Tamoxifen	56-65	TSC complex subunit 1	Mus musculus	39-43
30079598-7	2018	In contrast, postnatal inactivation of Tsc1 utilizing a tamoxifen-inducible Cx3cr1-CreER resulted in a more-selective microglia Tsc1 inactivation with high efficiency, mTORC1 activation, and increased microglial size and number, but no documented epilepsy.	Tamoxifen	56-65	TSC complex subunit 1	Mus musculus	128-132
30185506-3	2018	Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice.	Creatinine	143-153	TSC complex subunit 1	Mus musculus	12-40
30185506-3	2018	Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice.	Creatinine	143-153	TSC complex subunit 1	Mus musculus	42-46
30185506-3	2018	Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice.	Creatinine	143-153	TSC complex subunit 1	Mus musculus	101-105
30185506-3	2018	Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice.	Creatinine	143-153	TSC complex subunit 1	Mus musculus	101-105
30185506-3	2018	Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice.	Urea	164-168	TSC complex subunit 1	Mus musculus	12-40
30185506-3	2018	Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice.	Urea	164-168	TSC complex subunit 1	Mus musculus	42-46
30185506-3	2018	Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice.	Nitrogen	169-177	TSC complex subunit 1	Mus musculus	12-40
30185506-3	2018	Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice.	Nitrogen	169-177	TSC complex subunit 1	Mus musculus	42-46
29991473-9	2018	TSC1 deletion in the myeloid lineage constitutively activated mechanistic target of rapamycin complex 1 (mTORC1), increased M1 polarisation in synovial macrophages and exacerbated experimental OA in both CIOA and DMM models, while Rheb deletion inhibited mTORC1, enhanced M2 polarisation and alleviated CIOA in mice.	cioa	204-208	TSC complex subunit 1	Mus musculus	0-4
29991473-9	2018	TSC1 deletion in the myeloid lineage constitutively activated mechanistic target of rapamycin complex 1 (mTORC1), increased M1 polarisation in synovial macrophages and exacerbated experimental OA in both CIOA and DMM models, while Rheb deletion inhibited mTORC1, enhanced M2 polarisation and alleviated CIOA in mice.	dimethylmyleran	213-216	TSC complex subunit 1	Mus musculus	0-4
29991473-9	2018	TSC1 deletion in the myeloid lineage constitutively activated mechanistic target of rapamycin complex 1 (mTORC1), increased M1 polarisation in synovial macrophages and exacerbated experimental OA in both CIOA and DMM models, while Rheb deletion inhibited mTORC1, enhanced M2 polarisation and alleviated CIOA in mice.	cioa	303-307	TSC complex subunit 1	Mus musculus	0-4
29875165-5	2018	We found that in Pdx1-deficient mice, tuberous sclerosis 1 (Tsc1) ablation in pancreatic beta-cells restores beta-cell mass, increases beta-cell proliferation and size, decreases the number of TUNEL-positive cells and restores glucose tolerance after glucose challenge.	Glucose	227-234	TSC complex subunit 1	Mus musculus	38-58
29875165-5	2018	We found that in Pdx1-deficient mice, tuberous sclerosis 1 (Tsc1) ablation in pancreatic beta-cells restores beta-cell mass, increases beta-cell proliferation and size, decreases the number of TUNEL-positive cells and restores glucose tolerance after glucose challenge.	Glucose	227-234	TSC complex subunit 1	Mus musculus	60-64
30067967-8	2018	Notably, Tsc1 inactivation results in the accumulation of fumarate and in mTOR-dependent downregulation of the TCA cycle enzyme fumarate hydratase (FH).	Fumarates	58-66	TSC complex subunit 1	Mus musculus	9-13
28701517-5	2017	Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion.	Sirolimus	13-22	TSC complex subunit 1	Mus musculus	47-51
29635516-11	2018	These data establish roles for SAM-dependent methylation reactions and polyamine metabolism in TSC neuropathology.	Polyamines	71-80	TSC complex subunit 1	Mus musculus	95-98
28972182-7	2017	However, rapamycin further increased uPA expression in TSC2-null tumor cells and immortalized TSC2-null angiomyolipoma cells, but not in cells with intact TSC.	Sirolimus	9-18	TSC complex subunit 1	Mus musculus	55-58
28972182-10	2017	uPA-knock-out mice developed fewer and smaller TSC2-null lung tumors, and introduction of uPA shRNA in tumor cells or amiloride-induced uPA inhibition reduced tumorigenesis in vivo These findings suggest that interference with the uPA-dependent pathway, when used along with rapamycin, might attenuate LAM progression and potentially other TSC-related disorders.	Amiloride	118-127	TSC complex subunit 1	Mus musculus	47-50
29023667-5	2017	METHODS: An inducible Tsc1 knock-out mouse was created utilizing a tamoxifen-driven GFAP-CreER line (Tsc1GFAP-CreER mice) with TSC1 reduction induced postnatally at 2 and 6 weeks of age, and compared to conventional Tsc1GFAP-Cre mice with prenatal TSC1 reduction.	Tamoxifen	67-76	TSC complex subunit 1	Mus musculus	22-26
29023667-5	2017	METHODS: An inducible Tsc1 knock-out mouse was created utilizing a tamoxifen-driven GFAP-CreER line (Tsc1GFAP-CreER mice) with TSC1 reduction induced postnatally at 2 and 6 weeks of age, and compared to conventional Tsc1GFAP-Cre mice with prenatal TSC1 reduction.	Tamoxifen	67-76	TSC complex subunit 1	Mus musculus	127-131
29635516-1	2018	Tuberous sclerosis complex (TSC) is an autosomal dominant neurodevelopmental disorder and the quintessential disorder of mechanistic Target of Rapamycin Complex 1 (mTORC1) dysregulation.	Sirolimus	143-152	TSC complex subunit 1	Mus musculus	28-31
29483507-7	2018	Inhibition of glutamine metabolism in both Lkb1/Tsc1 and Pkd1 mutant mice significantly reduces cyst progression.	Glutamine	14-23	TSC complex subunit 1	Mus musculus	48-52
28808237-1	2017	Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1).	Sirolimus	179-188	TSC complex subunit 1	Mus musculus	96-100
28844017-0	2017	Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/- Mice.	Sirolimus	43-52	TSC complex subunit 1	Mus musculus	73-77
28844017-0	2017	Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/- Mice.	Atorvastatin	57-69	TSC complex subunit 1	Mus musculus	73-77
28959001-7	2017	The growth inhibitory effects of yangonin were attenuated inTSC1 or LKB1 knockout mouse embryonic fibroblasts, suggesting that TSC1 and LKB1 expression may contribute to optimal growth inhibition by yangonin.	yangonin	33-41	TSC complex subunit 1	Mus musculus	60-64
28520214-5	2017	Conversely, BMMs lacking Tsc1 exhibited a severe defect in osteoclast-like differentiation and absorptive function, both of which were restored following rapamycin treatment.	Sirolimus	154-163	TSC complex subunit 1	Mus musculus	25-29
28938574-9	2017	Further investigations are therefore needed to test whether rapamycin in combination with GSK2126458 could promote apoptosis and thus improve therapy of TSC-associated renal tumours.	omipalisib	90-100	TSC complex subunit 1	Mus musculus	153-156
28775826-0	2017	A brain proteomic investigation of rapamycin effects in the Tsc1+/- mouse model.	Sirolimus	35-44	TSC complex subunit 1	Mus musculus	60-64
28775826-3	2017	Heterozygocity induces hyperactivation of mTOR which can be inhibited by mTOR inhibitors, such as rapamycin, which have proven efficacy in the treatment of TSC-associated symptoms.	Sirolimus	98-107	TSC complex subunit 1	Mus musculus	156-159
28775826-4	2017	The aim of the present study was (1) to identify molecular changes associated with social and cognitive deficits in the brain tissue of Tsc1+/- mice and (2) to investigate the molecular effects of rapamycin treatment, which has been shown to ameliorate genotype-related behavioural deficits.	Sirolimus	197-206	TSC complex subunit 1	Mus musculus	136-140
28775826-13	2017	Rapamycin treatment exerted a stronger proteomic effect in Tsc1+/- mice with significant changes (mainly decreased expression) in 231 and 106 proteins, respectively.	Sirolimus	0-9	TSC complex subunit 1	Mus musculus	59-63
28775826-14	2017	The cellular pathways "oxidative stress" and "apoptosis" were found to be affected in Tsc1+/- mice and the cellular compartments "myelin sheet" and "neurofilaments" were affected by rapamycin treatment.	Sirolimus	182-191	TSC complex subunit 1	Mus musculus	86-90
28775826-15	2017	Thirty-three proteins which were altered in Tsc1+/- mice were normalized following rapamycin treatment, amongst them oxidative stress related proteins, myelin-specific and ribosomal proteins.	Sirolimus	83-92	TSC complex subunit 1	Mus musculus	44-48
28400571-6	2017	Tsc1 tg mice are more tolerant to exhaustive exercises and less susceptible to isoproterenol-induced cardiac hypertrophy at both young and advanced ages.	Isoproterenol	79-92	TSC complex subunit 1	Mus musculus	0-4
28400571-7	2017	Tsc1 tg mice have less fibrosis and inflammation in aged as well as isoproterenol-challenged heart than age-matched wild type mice.	Isoproterenol	68-81	TSC complex subunit 1	Mus musculus	0-4
27819329-8	2016	TSC1 CKO mice developed pronounced liver fibrosis relative to WT mice, as examined by ALT, hydroxyproline, histopathology, and profibrogenic gene.	Hydroxyproline	91-105	TSC complex subunit 1	Mus musculus	0-4
27524416-4	2017	Pituitary knockout of either mTOR signaling pathway negative regulator Tsc1 or Pten caused mouse pituitary prolactinoma, which was abolished by rapamycin treatment.	Sirolimus	144-153	TSC complex subunit 1	Mus musculus	71-75
28367235-5	2017	By analyzing Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs), we found that loss of TSC1 or TSC2 led to a decreased sensitivity to MK-2206, a novel allosteric Akt inhibitor.	MK 2206	137-144	TSC complex subunit 1	Mus musculus	13-17
28367235-5	2017	By analyzing Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs), we found that loss of TSC1 or TSC2 led to a decreased sensitivity to MK-2206, a novel allosteric Akt inhibitor.	MK 2206	137-144	TSC complex subunit 1	Mus musculus	90-94
27754935-6	2017	Neurogenin3-Tsc1-/- mice fed standard chow demonstrated a significant improvement in glucose tolerance and no alteration in insulin sensitivity.	Glucose	85-92	TSC complex subunit 1	Mus musculus	12-16
27754935-9	2017	TSC1-mTORC1 signaling plays an important role in the development of pancreatic endocrine cells and in the regulation of glucose metabolism.	Glucose	120-127	TSC complex subunit 1	Mus musculus	0-4
27519418-3	2016	In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production.	Oxygen	279-285	TSC complex subunit 1	Mus musculus	71-75
27519418-3	2016	In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production.	Adenosine Triphosphate	307-310	TSC complex subunit 1	Mus musculus	71-75
26296742-7	2016	Furthermore, pharmacologic treatment of Tsc1 single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6.	Sirolimus	69-78	TSC complex subunit 1	Mus musculus	40-44
27263494-9	2016	Minocycline treatment prevented the increase in number and cell size of microglia in 4-week-old Tsc1(GFAP) CKO mice.	Minocycline	0-11	TSC complex subunit 1	Mus musculus	96-100
27263494-11	2016	SIGNIFICANCE: Microglia cell number and size are abnormal in Tsc1(GFAP) CKO mice, and minocycline treatment inhibits this microglia activation, but does not suppress seizures.	Minocycline	86-97	TSC complex subunit 1	Mus musculus	61-65
27346353-6	2016	Mice with a double knockout of the insulin receptor and Tsc1 had larger livers, hyperglycemia, severely impaired glycogen storage, and suppressed ketogenesis, as compared to those with loss of the liver insulin receptor alone.	Glycogen	113-121	TSC complex subunit 1	Mus musculus	56-60
27387347-3	2016	RESULTS: In contrast to the previous studies using Tsc1 knockout mouse embryonic fibroblasts (MEF) cells, we demonstrated evidence that TSC1 deficient macrophages exhibited enhanced basal and mycobacterial infection-induced autophagy via AMPKalpha-dependent phosphorylation of ULK1 (Ser555).	ampkalpha	238-247	TSC complex subunit 1	Mus musculus	136-140
26923434-5	2016	Adipocyte Tsc1 deletion enhanced mitochondrial oxidative activity, fatty acid oxidation and the expression of PGC-1alpha and PPARalpha in both visceral and subcutaneous fat.	Fatty Acids	67-77	TSC complex subunit 1	Mus musculus	10-14
26923434-7	2016	Adipocyte Tsc1 deletion also reduced visceral adiposity and enhanced glucose tolerance, liver and muscle insulin signaling and adiponectin secretion in mice fed with purified low- or high-fat diet.	Glucose	69-76	TSC complex subunit 1	Mus musculus	10-14
26846849-9	2016	Following acute Tsc1 deletion from hepatocytes, Akt phosphorylation, but not IRS1/PI3K association, was rapidly restored by treatment with the mTORC1 inhibitor rapamycin.	Sirolimus	160-169	TSC complex subunit 1	Mus musculus	16-20
26873267-8	2016	In infants diagnosed prenatally with TSC, clusters of sharp waves or spikes preceded the first seizure, and vigabatrin prevented the development of seizures.	Vigabatrin	108-118	TSC complex subunit 1	Mus musculus	37-40
26991739-6	2016	Treatment with 5 mg/kg rapamycin for 3 weeks to inhibit mTORC1 and mTORC2 fully reversed PH in SM22-TSC1(-/-) mice.	Sirolimus	23-32	TSC complex subunit 1	Mus musculus	100-104
26991739-8	2016	Cultured PASMCs from SM22-TSC1(-/-), SM22-5HTT(+), and chronically hypoxic mice exhibited similar sustained growth-rate enhancement and constitutive mTORC1 and mTORC2 activation; both effects were abolished by rapamycin.	pasmcs	9-15	TSC complex subunit 1	Mus musculus	26-30
27362797-6	2016	Because cells with TSC loss fail to completely inhibit mTORC1 and properly activate autophagy in the absence of amino acids, we sporadically administered the mTORC1 inhibitor rapamycin, which was sufficient to correct the defects seen in cones, further enhancing the efficiency of cone survival mediated by Tsc1 loss.	Sirolimus	175-184	TSC complex subunit 1	Mus musculus	307-311
26122303-6	2015	Based on the Western blot studies, different dosing paradigms of rapamycin starting at postnatal day 21 were tested for their ability to prevent epilepsy or pathologic abnormalities in Tsc1(GFAP)CKO mice: 4 days of rapamycin only (4- ), 4 days on-24 days off (4-24), and 4 days on-10 days off (4-10).	Sirolimus	65-74	TSC complex subunit 1	Mus musculus	185-189
26921394-6	2016	In addition, we observed that bladder cancer cell lines (RT4, UMUC-3, and J82) with homozygous deletion of either TSC1 or PTEN are more sensitive to metformin than those (TEU2, TCCSUP, and HT1376) with wild-type TSC1 and PTEN genes.	Metformin	149-158	TSC complex subunit 1	Mus musculus	114-118
26921394-6	2016	In addition, we observed that bladder cancer cell lines (RT4, UMUC-3, and J82) with homozygous deletion of either TSC1 or PTEN are more sensitive to metformin than those (TEU2, TCCSUP, and HT1376) with wild-type TSC1 and PTEN genes.	Metformin	149-158	TSC complex subunit 1	Mus musculus	212-216
26655465-1	2016	Expression of hypoxia-inducible factor 1a (HIF1a) is increased under several pathological conditions such as hyperactive mechanistic target of rapamycin complex 1 (mTORC1) in tuberous sclerosis complex (TSC).	Sirolimus	143-152	TSC complex subunit 1	Mus musculus	203-206
26003087-7	2015	Epicatechin-3-gallate, an inhibitor of IL-1beta and CXCL10, at least partially reversed the elevated cytokine and chemokine levels, reduced seizure frequency, and prolonged survival of Tsc1(GFAP)CKO mice.	epicatechin gallate	0-21	TSC complex subunit 1	Mus musculus	185-189
26224859-6	2015	Importantly, transcripts for the activating transcription factor-3 (Atf3) and mitochondrial uncoupling protein-2 (Ucp2) are highly induced in Tsc2-deficient neurons, as well as in a neuron-specific Tsc1 conditional knock-out mouse model, and show differential responses to the mTOR inhibitor rapamycin.	Sirolimus	292-301	TSC complex subunit 1	Mus musculus	198-202
26795955-3	2016	Phosphorylated S6 was up-regulated in Tsc1(-/-) mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1(-/-) mammary epithelium.	Sirolimus	95-104	TSC complex subunit 1	Mus musculus	38-42
26795955-3	2016	Phosphorylated S6 was up-regulated in Tsc1(-/-) mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1(-/-) mammary epithelium.	Sirolimus	95-104	TSC complex subunit 1	Mus musculus	151-155
26795955-4	2016	The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development.	Sirolimus	21-30	TSC complex subunit 1	Mus musculus	59-63
26795955-4	2016	The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development.	Sirolimus	21-30	TSC complex subunit 1	Mus musculus	122-126
27746591-6	2016	Monocytes obtained from TSC1 KO mice produced more ROS, IL-6, IL-10, and TGF-beta and less IL-1, IFN-gamma, and TNF-alpha.	ros	51-54	TSC complex subunit 1	Mus musculus	24-28
26382847-3	2015	Doxycycline caused Tsc1 knock-down and consequently mTOR activation in AECs for the STT mice.	Doxycycline	0-11	TSC complex subunit 1	Mus musculus	19-23
26122303-9	2015	SIGNIFICANCE: Intermittent dosing of rapamycin, with drug holidays of more than 3 weeks, maintains significant antiepileptogenic properties in mouse models of TSC.	Sirolimus	37-46	TSC complex subunit 1	Mus musculus	159-162
25613864-1	2015	The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity.	Sirolimus	229-238	TSC complex subunit 1	Mus musculus	48-51
25613864-1	2015	The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity.	Sirolimus	229-238	TSC complex subunit 1	Mus musculus	134-138
25613864-1	2015	The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity.	Sirolimus	229-238	TSC complex subunit 1	Mus musculus	140-148
25613864-6	2015	Recently, glutamine has been shown to alter mTORC1 activity in a TSC1-TSC2 independent manner in cells cultured under amino acid- and serum-deprived conditions.	Glutamine	10-19	TSC complex subunit 1	Mus musculus	65-69
25613864-10	2015	Taken together, these results suggest that glutamine supplementation can be used as a potential treatment for TSC.	Glutamine	43-52	TSC complex subunit 1	Mus musculus	110-113
25646773-6	2015	Following 8 weeks of high-fat diet, the Tsc1-/-;S6k1-/- mice had lower body weights but higher liver TG levels compared to that of the Tsc1-/- mice.	Thioguanine	101-103	TSC complex subunit 1	Mus musculus	40-44
25646773-9	2015	However, liver TG levels were significantly reduced in the Tsc1-/-;Pten-/- mice compared to the Pten-/- mice, which was restored with rapamycin.	Sirolimus	134-143	TSC complex subunit 1	Mus musculus	59-63
25213336-8	2015	Rapamycin reversed the conversion from BAT to WAT in Fabp4-Tsc1(-/-) mice.	Sirolimus	0-9	TSC complex subunit 1	Mus musculus	59-63
23661807-8	2013	Similarly, mice with fibroblast-specific deletion of Tsc1, a negative regulator of Rheb, exhibited activated mTORC1 signaling in kidney interstitial fibroblasts and increased renal fibrosis, both of which rapamycin abolished.	Sirolimus	205-214	TSC complex subunit 1	Mus musculus	53-57
25288394-1	2014	Genetic studies have shown that the tuberous sclerosis complex (TSC) 1-TSC2-mammalian target of Rapamycin (mTOR) and the Hippo-Yes-associated protein 1 (YAP) pathways are master regulators of organ size, which are often involved in tumorigenesis.	Sirolimus	96-105	TSC complex subunit 1	Mus musculus	64-67
25082895-4	2014	L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner.	Triglycerides	83-95	TSC complex subunit 1	Mus musculus	0-9
25082895-4	2014	L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner.	Sirolimus	109-118	TSC complex subunit 1	Mus musculus	0-9
24203997-3	2014	We showed that mice with collecting-duct (CD)-specific ablation of TSC1 (CDTsc1KO) had greater mTOR complex 1 (mTORC1) activation in the CD and demonstrated features of pseudohypoaldosteronism, including hyperkalemia, hyperaldosteronism, and metabolic acidosis.	Cadmium	42-44	TSC complex subunit 1	Mus musculus	67-71
24203997-7	2014	Overall, this study identifies a novel function of mTORC1 in regulating potassium homeostasis and demonstrates that loss of TSC1 and activation of mTORC1 results in dedifferentiation and dysfunction of the CD and causes hyperkalemia.	Potassium	72-81	TSC complex subunit 1	Mus musculus	124-128
24203997-7	2014	Overall, this study identifies a novel function of mTORC1 in regulating potassium homeostasis and demonstrates that loss of TSC1 and activation of mTORC1 results in dedifferentiation and dysfunction of the CD and causes hyperkalemia.	Cadmium	206-208	TSC complex subunit 1	Mus musculus	124-128
24961618-8	2013	Furthermore, in striatal slices TSC1 reduced the inward currents induced by NMDA in medium-sized spiny neurons, demonstrating neuroprotection.	N-Methylaspartate	76-80	TSC complex subunit 1	Mus musculus	32-36
24961618-6	2013	In contrast, mice injected with NMDA + TSC1 proliferated twice as much indicating that TSC1 supported regeneration of the OLP population after the insult.	N-Methylaspartate	32-36	TSC complex subunit 1	Mus musculus	87-91
21941369-7	2012	Furthermore, transformed AMPK-/- and TSC1-/- MEFs both have higher total protein synthesis rates than wild-type controls, and translation inhibition using cycloheximide partially restores their anoikis resistance, indicating a mechanism whereby mTORC1 inhibition suppresses anoikis.	Cycloheximide	155-168	TSC complex subunit 1	Mus musculus	37-41
23228442-2	2013	Recent studies suggest that metformin attenuates mTORC1 signalling by the activation of 5" adenosine monophosphate-activated protein kinase (AMPK) in the presence or absence of a functional hamartin/tuberin (TSC1/TSC2) complex.	Metformin	28-37	TSC complex subunit 1	Mus musculus	208-212
23228442-7	2013	Metformin treatment appeared to attenuate mTORC1 signalling in Tsc1(+/-) kidney tissues but not in renal tumours.	Metformin	0-9	TSC complex subunit 1	Mus musculus	63-67
23228442-9	2013	Treatment of cultured cells derived from a Tsc1-associated renal tumour with 5-aza-2-deoxycytidine or trichostatin A greatly increased the expression of these genes.	Decitabine	77-98	TSC complex subunit 1	Mus musculus	43-47
23228442-9	2013	Treatment of cultured cells derived from a Tsc1-associated renal tumour with 5-aza-2-deoxycytidine or trichostatin A greatly increased the expression of these genes.	trichostatin A	102-116	TSC complex subunit 1	Mus musculus	43-47
23228442-10	2013	These data suggest that the epigenetic suppression of the organic cation transporters in Tsc-associated mouse renal tumours may contribute to the lack of response to metformin treatment.	Metformin	166-175	TSC complex subunit 1	Mus musculus	89-92
23143994-5	2013	Maternal administration of rapamycin, a classical mTOR inhibitor, significantly increased the survival time of Fabp4-Tsc1cKO mice for up to 23 days.	Sirolimus	27-36	TSC complex subunit 1	Mus musculus	117-121
23386687-3	2013	Rapamycin and related drugs have been shown to have clinical benefit for these tumors in patients with TSC and those with sporadic forms of TSC-related neoplasms.	Sirolimus	0-9	TSC complex subunit 1	Mus musculus	103-106
23386687-3	2013	Rapamycin and related drugs have been shown to have clinical benefit for these tumors in patients with TSC and those with sporadic forms of TSC-related neoplasms.	Sirolimus	0-9	TSC complex subunit 1	Mus musculus	140-143
23386687-10	2013	Differences in side-effect profiles might make MLN0128 more attractive for treatment of patients with TSC-related tumors, but will require additional study in humans.	INK128	47-54	TSC complex subunit 1	Mus musculus	102-105
23335988-9	2013	In addition, rapamycin, a specific mTORC1 inhibitor, effectively rescued the phenotype caused by increased mTORC1 activity in the Tsc1(cko) ovaries.	Sirolimus	13-22	TSC complex subunit 1	Mus musculus	130-134
21890496-4	2011	These observations have led us to examine the benefit of prenatal rapamycin in a new fetal brain model of TSC.	Sirolimus	66-75	TSC complex subunit 1	Mus musculus	106-109
23049940-5	2012	We then tested the tamoxifen-inducible recombinase activity of Cre-ER(T2) in a mouse strain bearing TSC1 conditional knockout alleles (TSC1(fx/fx)).	Tamoxifen	19-28	TSC complex subunit 1	Mus musculus	100-104
23049940-5	2012	We then tested the tamoxifen-inducible recombinase activity of Cre-ER(T2) in a mouse strain bearing TSC1 conditional knockout alleles (TSC1(fx/fx)).	Tamoxifen	19-28	TSC complex subunit 1	Mus musculus	135-139
23049940-6	2012	TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ER(T2)/TSC1(fx/fx) mice.	Tamoxifen	43-52	TSC complex subunit 1	Mus musculus	0-4
23049940-6	2012	TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ER(T2)/TSC1(fx/fx) mice.	Tamoxifen	43-52	TSC complex subunit 1	Mus musculus	76-80
21890496-10	2011	These observations demonstrate the therapeutic benefit and limitations of prenatal rapamycin in a prenatal-onset brain model of TSC.	Sirolimus	83-92	TSC complex subunit 1	Mus musculus	128-131
21212099-0	2011	Smooth muscle protein-22-mediated deletion of Tsc1 results in cardiac hypertrophy that is mTORC1-mediated and reversed by rapamycin.	Sirolimus	122-131	TSC complex subunit 1	Mus musculus	46-50
22018000-3	2011	In particular, cells with constitutive mTORC1 activity secondary to the loss of TSC1/TSC2 function are prone to undergo apoptosis upon glucose withdrawal in vitro, but this concept has not been tested in vivo.	Glucose	135-142	TSC complex subunit 1	Mus musculus	80-84
21179166-6	2010	We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting-resistant increase in liver size, and to a pronounced defect in ketone body production and ketogenic gene expression on fasting.	Ketones	169-175	TSC complex subunit 1	Mus musculus	36-40
21062901-7	2011	The differences between Tsc1(GFAP1)CKO and Tsc2(GFAP1)CKO mice were correlated with higher levels of mammalian target of rapamycin (mTOR) activation in Tsc2(GFAP1)CKO mice and were reversed by the mTOR inhibitor, rapamycin.	Sirolimus	121-130	TSC complex subunit 1	Mus musculus	24-28
21179166-6	2010	We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting-resistant increase in liver size, and to a pronounced defect in ketone body production and ketogenic gene expression on fasting.	Ketones	169-175	TSC complex subunit 1	Mus musculus	42-62
20851890-5	2010	RSV treatment also partially blocked mTOR and S6 kinase phosphorylation in TSC1/2-deficient mouse embryonic fibroblasts, suggesting the presence of an inhibitory site downstream of TSC1/2.	Resveratrol	0-3	TSC complex subunit 1	Mus musculus	75-79
20851890-5	2010	RSV treatment also partially blocked mTOR and S6 kinase phosphorylation in TSC1/2-deficient mouse embryonic fibroblasts, suggesting the presence of an inhibitory site downstream of TSC1/2.	Resveratrol	0-3	TSC complex subunit 1	Mus musculus	75-81
19385061-3	2009	Correspondingly, hippocampal slices from Tsc1(GFAP)CKO mice have increased extracellular potassium concentration in response to stimulation.	Potassium	89-98	TSC complex subunit 1	Mus musculus	41-45
20045054-2	2010	In particular, decreased expression and function of astrocyte glutamate transporters have been implicated in causing elevated extracellular glutamate levels, neuronal death, and epilepsy in a mouse model of TSC (Tsc1(GFAP)CKO mice), involving inactivation of the Tsc1 gene primarily in astrocytes.	Glutamic Acid	62-71	TSC complex subunit 1	Mus musculus	212-216
20045054-2	2010	In particular, decreased expression and function of astrocyte glutamate transporters have been implicated in causing elevated extracellular glutamate levels, neuronal death, and epilepsy in a mouse model of TSC (Tsc1(GFAP)CKO mice), involving inactivation of the Tsc1 gene primarily in astrocytes.	Glutamic Acid	62-71	TSC complex subunit 1	Mus musculus	263-267
20045054-4	2010	Early treatment with ceftriaxone prior to the onset of epilepsy increased expression of astrocyte glutamate transporters, decreased extracellular glutamate levels, neuronal death, and seizure frequency, and improved survival in Tsc1(GFAP)CKO mice.	Ceftriaxone	21-32	TSC complex subunit 1	Mus musculus	228-232
19738049-4	2009	We observed the same characteristics in wild-type primary cultures of CGNPs in which TSC1 and/or TSC2 were knocked down, and in mouse medulloblastomas induced by ectopic Shh pathway activation.	cgnps	70-75	TSC complex subunit 1	Mus musculus	85-89
19385061-6	2009	These findings suggest that Tsc1 inactivation in astrocytes causes defects in astrocytic gap junction coupling and potassium clearance, which may contribute to epilepsy in Tsc1(GFAP)CKO mice.	Potassium	115-124	TSC complex subunit 1	Mus musculus	28-32
17290308-4	2007	This was a direct effect of mTOR activation, since rapamycin restored PDGFR expression and PDGF-sensitive Akt activation in Tsc1-/- and Tsc2-/- cells.	Sirolimus	51-60	TSC complex subunit 1	Mus musculus	124-128
19368729-3	2009	Early clinical trials show that TSC-related kidney tumors (angiomyolipomas) regress when treated with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (also known as sirolimus).	Sirolimus	126-135	TSC complex subunit 1	Mus musculus	32-35
19368729-3	2009	Early clinical trials show that TSC-related kidney tumors (angiomyolipomas) regress when treated with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (also known as sirolimus).	Sirolimus	179-188	TSC complex subunit 1	Mus musculus	32-35
19368729-6	2009	RESULTS: Here, we examine the efficacy of a prolonged maintenance dose of rapamycin in Tsc2+/- mice with TSC-related kidney tumors.	Sirolimus	74-83	TSC complex subunit 1	Mus musculus	105-108
18511518-9	2008	The effect of mTORC1 on glucose uptake was confirmed using a liver-specific Tsc1- deletion mouse model in which FDG uptake was reduced in the livers of mutant mice compared with wild-type controls.	Glucose	24-31	TSC complex subunit 1	Mus musculus	76-80
17714952-1	2007	Mice with inactivation of the Tuberous sclerosis complex-1 (Tsc1) gene in glia (Tsc1 GFAP CKO mice) have deficient astrocyte glutamate transporters and develop seizures, suggesting that abnormal glutamate homeostasis contributes to neurological abnormalities in these mice.	Glutamic Acid	125-134	TSC complex subunit 1	Mus musculus	30-58
17714952-1	2007	Mice with inactivation of the Tuberous sclerosis complex-1 (Tsc1) gene in glia (Tsc1 GFAP CKO mice) have deficient astrocyte glutamate transporters and develop seizures, suggesting that abnormal glutamate homeostasis contributes to neurological abnormalities in these mice.	Glutamic Acid	125-134	TSC complex subunit 1	Mus musculus	60-64
17714952-1	2007	Mice with inactivation of the Tuberous sclerosis complex-1 (Tsc1) gene in glia (Tsc1 GFAP CKO mice) have deficient astrocyte glutamate transporters and develop seizures, suggesting that abnormal glutamate homeostasis contributes to neurological abnormalities in these mice.	Glutamic Acid	125-134	TSC complex subunit 1	Mus musculus	80-84
17714952-2	2007	We examined the hypothesis that Tsc1 GFAP CKO mice have elevated extracellular brain glutamate levels that may cause neuronal death, abnormal glutamatergic synaptic function, and associated impairments in behavioral learning.	Glutamic Acid	85-94	TSC complex subunit 1	Mus musculus	32-36
17714952-3	2007	In vivo microdialysis documented elevated glutamate levels in hippocampi of Tsc1 GFAP CKO mice and several cell death assays demonstrated neuronal death in hippocampus and neocortex.	Glutamic Acid	42-51	TSC complex subunit 1	Mus musculus	76-80
17714952-4	2007	Impairment of long-term potentiation (LTP) with tetanic stimulation was observed in hippocampal slices from Tsc1 GFAP CKO mice and was reversed by low concentrations of NMDA antagonist, indicating that excessive synaptic glutamate directly inhibited LTP.	N-Methylaspartate	169-173	TSC complex subunit 1	Mus musculus	108-112
17714952-6	2007	These results suggest that abnormal glutamate homeostasis predisposes to excitotoxic cell death, impaired synaptic plasticity and learning deficits in Tsc1 GFAP CKO mice.	Glutamic Acid	36-45	TSC complex subunit 1	Mus musculus	151-155
18949383-4	2008	In the present study, we demonstrated that TNFalpha-IKKbeta-mediated inactivation of TSC1 resulted in increasing phosphorylation of IRS1 serine 307 and serine 636/639, impaired insulin-induced glucose uptake, tyrosine phosphorylation of IRS1, and the association between IRS1 and PI3K p85.	Serine	137-143	TSC complex subunit 1	Mus musculus	85-89
18949383-4	2008	In the present study, we demonstrated that TNFalpha-IKKbeta-mediated inactivation of TSC1 resulted in increasing phosphorylation of IRS1 serine 307 and serine 636/639, impaired insulin-induced glucose uptake, tyrosine phosphorylation of IRS1, and the association between IRS1 and PI3K p85.	Serine	152-158	TSC complex subunit 1	Mus musculus	85-89
18949383-4	2008	In the present study, we demonstrated that TNFalpha-IKKbeta-mediated inactivation of TSC1 resulted in increasing phosphorylation of IRS1 serine 307 and serine 636/639, impaired insulin-induced glucose uptake, tyrosine phosphorylation of IRS1, and the association between IRS1 and PI3K p85.	Tyrosine	209-217	TSC complex subunit 1	Mus musculus	85-89
18389497-5	2008	METHODS: Tsc1(GFAP)CKO mice and littermate control animals were treated with rapamycin or vehicle starting at postnatal day 14 (early treatment) or 6 weeks of age (late treatment), corresponding to times before and after onset of neurological abnormalities in Tsc1(GFAP)CKO mice.	Sirolimus	77-86	TSC complex subunit 1	Mus musculus	9-13
18389497-9	2008	RESULTS: Early treatment with rapamycin prevented the development of epilepsy and premature death observed in vehicle-treated Tsc1(GFAP)CKO mice.	Sirolimus	30-39	TSC complex subunit 1	Mus musculus	126-130
18389497-10	2008	Late treatment with rapamycin suppressed seizures and prolonged survival in Tsc1(GFAP)CKO mice that had already developed epilepsy.	Sirolimus	20-29	TSC complex subunit 1	Mus musculus	76-80
18389497-12	2008	INTERPRETATION: Rapamycin has strong efficacy for preventing seizures and prolonging survival in Tsc1(GFAP)CKO mice.	Sirolimus	16-25	TSC complex subunit 1	Mus musculus	97-101
16845661-3	2006	The mTOR inhibitor, rapamycin (sirolimus), reduces disease severity in rodent models of TSC, and is currently in phase II clinical trials.	Sirolimus	20-29	TSC complex subunit 1	Mus musculus	88-91
16845661-3	2006	The mTOR inhibitor, rapamycin (sirolimus), reduces disease severity in rodent models of TSC, and is currently in phase II clinical trials.	Sirolimus	31-40	TSC complex subunit 1	Mus musculus	88-91
16393152-4	2005	Here, we investigated the hypothesis that impairment of potassium uptake through astrocyte inward rectifier potassium (Kir) channels may contribute to epileptogenesis in Tsc1(GFAP)CKO mice.	Potassium	56-65	TSC complex subunit 1	Mus musculus	170-174
16393152-11	2005	Last, hippocampal slices from Tsc1(GFAP)CKO mice exhibited decreased astrocytic Kir currents, as well as increased susceptibility to potassium-induced epileptiform activity.	Potassium	133-142	TSC complex subunit 1	Mus musculus	30-34
15150095-2	2004	We demonstrate a dramatic decrease of IFN-gamma expression in tumors and mouse embryo fibroblast cell lines that lack either Tsc1 or Tsc2, which is reversed by rapamycin (mammalian target of rapamycin inhibitor) therapy.	Sirolimus	160-169	TSC complex subunit 1	Mus musculus	125-129
15781664-7	2005	In contrast, tamoxifen treatment for 9 months significantly reduced the frequency and severity of hemangiomas in Tsc1+/- female mice.	Tamoxifen	13-22	TSC complex subunit 1	Mus musculus	113-117
14500340-6	2003	Moreover, short-term treatment of Tsc1+/- mice with rapamycin at 20 mg/kg led to some changes in tumor morphology and a reduction in serum VEGF levels.	Sirolimus	52-61	TSC complex subunit 1	Mus musculus	34-38
14718525-0	2004	Tsc1+ and tsc2+ regulate arginine uptake and metabolism in Schizosaccharomyces pombe.	Arginine	25-33	TSC complex subunit 1	Mus musculus	0-4
14718525-3	2004	Here we show that S. pombe lacking tsc1+ or tsc2+ have similar phenotypes including decreased arginine uptake, decreased expression of three amino acid permeases, and low intracellular levels of four members of the arginine biosynthesis pathway.	Arginine	94-102	TSC complex subunit 1	Mus musculus	35-39
14718525-3	2004	Here we show that S. pombe lacking tsc1+ or tsc2+ have similar phenotypes including decreased arginine uptake, decreased expression of three amino acid permeases, and low intracellular levels of four members of the arginine biosynthesis pathway.	Arginine	215-223	TSC complex subunit 1	Mus musculus	35-39
14718525-7	2004	Taken together, these findings support a model in which arginine uptake is regulated through tsc1+, tsc2+, and rhb1+ in S. pombe and also suggest a role for the Tsc1 and Tsc2 proteins in amino acid biosynthesis and sensing.	Arginine	56-64	TSC complex subunit 1	Mus musculus	93-97
12891680-5	2003	Electrophysiological assays demonstrate a functional decrease in glutamate transport currents of Tsc1 cKO astrocytes in hippocampal slices and astrocyte cultures.	Glutamic Acid	65-74	TSC complex subunit 1	Mus musculus	97-101
11875047-6	2002	Tsc1 null embryo fibroblast lines have persistent phosphorylation of the p70S6K (S6K) and its substrate S6, that is sensitive to treatment with rapamycin, indicating constitutive activation of the mTOR-S6K pathway due to loss of the Tsc1 protein, hamartin.	Sirolimus	144-153	TSC complex subunit 1	Mus musculus	0-4
11875047-6	2002	Tsc1 null embryo fibroblast lines have persistent phosphorylation of the p70S6K (S6K) and its substrate S6, that is sensitive to treatment with rapamycin, indicating constitutive activation of the mTOR-S6K pathway due to loss of the Tsc1 protein, hamartin.	Sirolimus	144-153	TSC complex subunit 1	Mus musculus	233-237
11875047-6	2002	Tsc1 null embryo fibroblast lines have persistent phosphorylation of the p70S6K (S6K) and its substrate S6, that is sensitive to treatment with rapamycin, indicating constitutive activation of the mTOR-S6K pathway due to loss of the Tsc1 protein, hamartin.	Sirolimus	144-153	TSC complex subunit 1	Mus musculus	247-255