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Appears in Networks 13

In-Edges 8

Out-Edges 50

a(CHEBI:sirolimus) decreases bp(HBP:"PI3K-Akt signaling pathway") View Subject | View Object

Genes in the mTOR pathway were also of specific interest because this pathway is inhibited by the immunosuppressant drug rapamy- cin via complex formation with FKBP1b/1a. PubMed:29255009

a(CHEBI:sirolimus) decreases act(p(FPLX:mTORC1)) View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

Annotations
Cell Ontology (CL)
motor neuron

a(CHEBI:sirolimus) decreases path(MESH:"Protein Aggregation, Pathological") View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

Annotations
Cell Ontology (CL)
motor neuron

a(CHEBI:sirolimus) decreases path(MESH:"Huntington Disease") View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

Annotations
Cell Ontology (CL)
motor neuron

a(CHEBI:sirolimus) decreases path(MESH:"Machado-Joseph Disease") View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

Annotations
Cell Ontology (CL)
motor neuron

a(CHEBI:sirolimus) decreases path(MESH:"Alzheimer Disease") View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

Annotations
Cell Ontology (CL)
motor neuron

a(CHEBI:sirolimus) decreases path(MESH:"Parkinson Disease") View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

Annotations
Cell Ontology (CL)
motor neuron

a(CHEBI:sirolimus) decreases path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

Annotations
Cell Ontology (CL)
motor neuron

a(CHEBI:sirolimus) decreases bp(GO:"TOR signaling") View Subject | View Object

We treated these neurons with staurosporine, a broad-spectrum kinase inhibitor that induces apoptosis (Budd et al., 2000); rotenone, a complex inhibitor that induces mitochondrial dysfunction (Sherer et al., 2003); and rapamycin, an inhibitor of the mammalian target of the rapamycin (mTOR) signaling pathway with many downstream effects (Li et al., 2014) PubMed:27594586

a(CHEBI:sirolimus) increases r(HGNC:MMP9) View Subject | View Object

MMP-9/MMP-2 mRNA levels in tau-A152T and MAPT IVS10+16 neurons were significantly higher than that in control neurons (Figure S2J), and rapamycin increased these levels (p < 0.01) (Figure 3C) PubMed:27594586

a(CHEBI:sirolimus) increases r(HGNC:MMP2) View Subject | View Object

MMP-9/MMP-2 mRNA levels in tau-A152T and MAPT IVS10+16 neurons were significantly higher than that in control neurons (Figure S2J), and rapamycin increased these levels (p < 0.01) (Figure 3C) PubMed:27594586

a(CHEBI:sirolimus) increases bp(GO:autophagy) View Subject | View Object

Enhancing auto- phagy with rapamycin reduced levels of α-synuclein, FUS and Htt 130–132 . PubMed:30116051

a(CHEBI:sirolimus) decreases p(HGNC:SNCA) View Subject | View Object

Enhancing auto- phagy with rapamycin reduced levels of α-synuclein, FUS and Htt 130–132 . PubMed:30116051

a(CHEBI:sirolimus) decreases p(HGNC:FUS) View Subject | View Object

Enhancing auto- phagy with rapamycin reduced levels of α-synuclein, FUS and Htt 130–132 . PubMed:30116051

a(CHEBI:sirolimus) decreases p(HGNC:HTT) View Subject | View Object

Enhancing auto- phagy with rapamycin reduced levels of α-synuclein, FUS and Htt 130–132 . PubMed:30116051

a(CHEBI:sirolimus) increases bp(MESH:Autophagy) View Subject | View Object

Stimulating autophagy either through serum withdrawal or rapamycin treatment in SH-SY5Y cells overexpressing P301L tau that had been induced to aggregate led to substantial reduction in aggregates that was prevented by 3-MA (70). PubMed:24027553

a(CHEBI:sirolimus) increases deg(p(HGNC:MAPT)) View Subject | View Object

Autophagy inducers, including rapamycin (Fig. 3A), facilitate the degradation of insoluble forms of tau and also protect against its toxicity in Drosophila (Berger et al., 2006). PubMed:23528736

a(CHEBI:sirolimus) increases bp(GO:macroautophagy) View Subject | View Object

A quite different strategy is to target tau clearance—e.g., by rapamycin that induces macroautophagy [175], inhibitors of Hsp90 chaperone protein that binds to misfolded proteins or by immunotherapeutic approaches [176]. PubMed:26751493

a(CHEBI:sirolimus) increases bp(GO:autophagy) View Subject | View Object

Wogonin, rapamycin, and temsirolimus have been considered to improve the activity of autophagy to increase Aβ clearance and inhibit tau phosphorylation via targeting mTOR signaling (Caccamo et al. 2010; Jiang et al. 2014c; Jiang et al. 2014d; Spilman et al. 2010; Zhu andWang 2015) PubMed:29626319

a(CHEBI:sirolimus) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Wogonin, rapamycin, and temsirolimus have been considered to improve the activity of autophagy to increase Aβ clearance and inhibit tau phosphorylation via targeting mTOR signaling (Caccamo et al. 2010; Jiang et al. 2014c; Jiang et al. 2014d; Spilman et al. 2010; Zhu andWang 2015) PubMed:29626319

a(CHEBI:sirolimus) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Wogonin, rapamycin, and temsirolimus have been considered to improve the activity of autophagy to increase Aβ clearance and inhibit tau phosphorylation via targeting mTOR signaling (Caccamo et al. 2010; Jiang et al. 2014c; Jiang et al. 2014d; Spilman et al. 2010; Zhu andWang 2015) PubMed:29626319

a(CHEBI:sirolimus) decreases act(p(HGNC:MTOR)) View Subject | View Object

For instance, rapamycin, an inhibitor of the Ser/Thr protein kinase mammalian target of rapamycin (mTOR), improves cognitive function and reduces Aβ in AD mouse model by enhancing autophagic flux [23]. PubMed:29758300

a(CHEBI:sirolimus) increases bp(GO:cognition) View Subject | View Object

For instance, rapamycin, an inhibitor of the Ser/Thr protein kinase mammalian target of rapamycin (mTOR), improves cognitive function and reduces Aβ in AD mouse model by enhancing autophagic flux [23]. PubMed:29758300

a(CHEBI:sirolimus) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

For instance, rapamycin, an inhibitor of the Ser/Thr protein kinase mammalian target of rapamycin (mTOR), improves cognitive function and reduces Aβ in AD mouse model by enhancing autophagic flux [23]. PubMed:29758300

a(CHEBI:sirolimus) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

For instance, while accumulation of Aβ activates the mTOR signaling pathway and subsequently blocks macroautophagy, rapamycin reduces the Aβ load by enhancing macroautophagy [32] PubMed:29758300

a(CHEBI:sirolimus) increases bp(GO:autophagy) View Subject | View Object

For instance, rapamycin, an inhibitor of the Ser/Thr protein kinase mammalian target of rapamycin (mTOR), improves cognitive function and reduces Aβ in AD mouse model by enhancing autophagic flux [23]. PubMed:29758300

a(CHEBI:sirolimus) increases bp(GO:macroautophagy) View Subject | View Object

For instance, while accumulation of Aβ activates the mTOR signaling pathway and subsequently blocks macroautophagy, rapamycin reduces the Aβ load by enhancing macroautophagy [32] PubMed:29758300

a(CHEBI:sirolimus) increases bp(GO:macroautophagy) View Subject | View Object

Protein clearance in animal models has been successfully demonstrated using several small molecules and drugs that enhance induction of macroautophagy reduces AD-relevant pathology, including rapamycin in 3xTGAD mice [32] and temsirolimus in P301S transgenic mice [156] and trehalose in APP/PS1 and P301S MAPT transgenic mice [157,158]. PubMed:29758300

a(CHEBI:sirolimus) decreases p(HGNC:MAPT) View Subject | View Object

Modulation of mTOR can influence the levels of tau, with upregulation increasing tau phosphorylation and accumulation by reducing autophagic clearance [87], and conversely, pharmacological treatment with rapamycin reducing tau levels and rescuing motor deficits in the Tau P301S mice [53] PubMed:29758300

a(CHEBI:sirolimus) increases bp(GO:"motor behavior") View Subject | View Object

Modulation of mTOR can influence the levels of tau, with upregulation increasing tau phosphorylation and accumulation by reducing autophagic clearance [87], and conversely, pharmacological treatment with rapamycin reducing tau levels and rescuing motor deficits in the Tau P301S mice [53] PubMed:29758300

a(CHEBI:sirolimus) increases bp(GO:autophagy) View Subject | View Object

Chronic low-level stimulation of autophagy through peripheral administration of rapamycin or other agents (Tian et al. 2011), or enhancing lysosomal proteolysis selectively (Sun et al. 2008; Yang et al. 2011), can markedly diminish Ab levels and amyloid load in APP transgenic mice, underscoring the importance of lysosomal clearance of Ab. PubMed:22908190

a(CHEBI:sirolimus) increases bp(GO:autophagy) View Subject | View Object

Consistent with these findings, rapamycin induction of autophagy reduces tau pathology in the triple transgenic AD-mouse model (Caccamo et al. 2010), whereas in other models, autophagic–lysosomal dysfunction amplifies tau pathology and tau neurotoxicity (Hamano et al. 2008; Khurana et al. 2010). PubMed:22908190

a(CHEBI:sirolimus) decreases path(MESH:Tauopathies) View Subject | View Object

Consistent with these findings, rapamycin induction of autophagy reduces tau pathology in the triple transgenic AD-mouse model (Caccamo et al. 2010), whereas in other models, autophagic–lysosomal dysfunction amplifies tau pathology and tau neurotoxicity (Hamano et al. 2008; Khurana et al. 2010). PubMed:22908190

a(CHEBI:sirolimus) decreases path(MESH:Tauopathies) View Subject | View Object

Peripheral administration of rapamycin to strongly stimulate autophagy substantially reduces amyloid deposition and tau pathology in both APPand triple transgenic mouse models of AD pathology (Caccamo et al. 2010; Spilman et al. 2010; Tian et al. 2011) PubMed:22908190

a(CHEBI:sirolimus) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Peripheral administration of rapamycin to strongly stimulate autophagy substantially reduces amyloid deposition and tau pathology in both APPand triple transgenic mouse models of AD pathology (Caccamo et al. 2010; Spilman et al. 2010; Tian et al. 2011) PubMed:22908190

a(CHEBI:sirolimus) decreases act(p(HGNC:MTOR)) View Subject | View Object

Pharmacological upregulation of autophagy can be accomplished using the drug rapamycin, which works by inhibiting TOR (target of rapamycin), a pleiotropic molecule that negatively regulates autophagy, among other functions PubMed:18930136

a(CHEBI:sirolimus) increases bp(GO:autophagy) View Subject | View Object

Pharmacological upregulation of autophagy can be accomplished using the drug rapamycin, which works by inhibiting TOR (target of rapamycin), a pleiotropic molecule that negatively regulates autophagy, among other functions PubMed:18930136

a(CHEBI:sirolimus) decreases path(MESH:"Bulbo-Spinal Atrophy, X-Linked") View Subject | View Object

Indeed, treatment with rapamycin ameliorates the degenerative phenotype in a Drosophila model of SBMA, as well as in Drosophila and mouse models of Huntington’s disease [48,50,52]. PubMed:18930136

a(CHEBI:sirolimus) decreases path(MESH:"Huntington Disease") View Subject | View Object

Indeed, treatment with rapamycin ameliorates the degenerative phenotype in a Drosophila model of SBMA, as well as in Drosophila and mouse models of Huntington’s disease [48,50,52]. PubMed:18930136

a(CHEBI:sirolimus) decreases act(p(HGNC:MTOR)) View Subject | View Object

Again, rapamycin and rapalogs protect against toxicity produced by a number of misfolded proteins encompassing alpha synuclein, TDP43, and hyperphosphorylated tau PubMed:30061532

a(CHEBI:sirolimus) decreases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Again, rapamycin and rapalogs protect against toxicity produced by a number of misfolded proteins encompassing alpha synuclein, TDP43, and hyperphosphorylated tau PubMed:30061532

a(CHEBI:sirolimus) decreases p(HGNC:SNCA, pmod(HBP:misfolded)) View Subject | View Object

Again, rapamycin and rapalogs protect against toxicity produced by a number of misfolded proteins encompassing alpha synuclein, TDP43, and hyperphosphorylated tau PubMed:30061532

a(CHEBI:sirolimus) decreases p(HGNC:TARDBP, pmod(HBP:misfolded)) View Subject | View Object

Again, rapamycin and rapalogs protect against toxicity produced by a number of misfolded proteins encompassing alpha synuclein, TDP43, and hyperphosphorylated tau PubMed:30061532

a(CHEBI:sirolimus) increases path(MESH:"Interpersonal Relations") View Subject | View Object

This is further supported by mounting evidence obtained in rodent models, which demonstrate that rapamycin normalizes impaired social interactions and reverses behavioral defects PubMed:30061532

a(CHEBI:sirolimus) increases bp(GO:behavior) View Subject | View Object

This is further supported by mounting evidence obtained in rodent models, which demonstrate that rapamycin normalizes impaired social interactions and reverses behavioral defects PubMed:30061532

a(CHEBI:sirolimus) decreases act(a(CHEBI:methamphetamine)) View Subject | View Object

In fact, mTOR-induced autophagy inhibition exacerbates the ultrastructural effects of METH [126,134–136], while rapamycin administration reverts both behavioral and morphological alterations induced by METH [137]. PubMed:30061532

a(CHEBI:sirolimus) decreases path(MESH:"Psychotic Disorders") View Subject | View Object

Likewise, rapamycin was found to be beneficial for ameliorating psychotic symptoms PubMed:30061532

a(CHEBI:sirolimus) decreases path(MESH:"Psychotic Disorders") View Subject | View Object

These pieces of evidence corroborate findings showing that several autophagy inducers, such as lithium, rapamycin, and Food and Drug Administration (FDA) approved antipsychotic drugs are effective to treat psychosis including schizophrenia PubMed:30061532

a(CHEBI:sirolimus) increases bp(GO:autophagy) View Subject | View Object

Noteworthy, genetic ablation of autophagy was shown to produce an extremely powerful DA release upon electrical stimuli, suggesting that autophagy is key to restrain DA release both upon basal neural activity and mostly after rapamycin-induced autophagy PubMed:30061532

a(CHEBI:sirolimus) decreases path(MESH:Schizophrenia) View Subject | View Object

These pieces of evidence corroborate findings showing that several autophagy inducers, such as lithium, rapamycin, and Food and Drug Administration (FDA) approved antipsychotic drugs are effective to treat psychosis including schizophrenia PubMed:30061532

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.