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p(HGNC:MTOR)

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Entity

Name
MTOR
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 5

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease v1.0.0

Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection v1.0.0

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders v1.0.0

Activity-dependent neuroprotective protein deficiency models synaptic and developmental phenotypes of autism-like syndrome v1.0.0

In-Edges 32

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

Appears in Networks:

bp(GO:autophagy) negativeCorrelation p(HGNC:MTOR) 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

Appears in Networks:

composite(p(FPLX:AMPK), p(HGNC:TSC2)) decreases act(p(HGNC:MTOR)) View Subject | View Object

For instance, adenosine monophosphate- activated protein kinase (AMPK) phosphorylates ULK1 and inactivates mTOR through the raptor and tuberous sclerosis complex (TSC2). PubMed:29758300

Appears in Networks:

p(HGNC:MAPT, pmod(Ph)) positiveCorrelation p(HGNC:MTOR) 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

Appears in Networks:

a(CHEBI:"insulin (human)") regulates p(HGNC:MTOR) View Subject | View Object

Induction of autophagy is generally controlled by the mTOR kinase (mammalian Target of Rapamycin), which is regulated by growth factors (especially insulin) and nutrient levels. PubMed:22908190

Appears in Networks:

bp(GO:"response to nutrient") regulates p(HGNC:MTOR) View Subject | View Object

Induction of autophagy is generally controlled by the mTOR kinase (mammalian Target of Rapamycin), which is regulated by growth factors (especially insulin) and nutrient levels. PubMed:22908190

Appears in Networks:

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

Appears in Networks:

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

In contrast, chlorpromazine, which is a typical antipsychotic agent, induces autophagy by inhibiting the Akt/mTOR pathway PubMed:30061532

Appears in Networks:

a(CHEBI:"lithium(1+)") decreases act(p(HGNC:MTOR)) View Subject | View Object

In fact, lithium is able to delay METH-induced sensitization, while being a powerful treatment in schizophrenia PubMed:30061532

Appears in Networks:

a(CHEBI:"mTOR inhibitor") 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

Appears in Networks:

a(CHEBI:methamphetamine) increases act(p(HGNC:MTOR)) View Subject | View Object

Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532

Appears in Networks:

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

Appears in Networks:

bp(GO:autophagy) negativeCorrelation act(p(HGNC:MTOR)) View Subject | View Object

Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532

Appears in Networks:

bp(GO:autophagy) regulates act(p(HGNC:MTOR)) View Subject | View Object

The relevance of autophagy for sustaining these mTOR-induced effects is confirmed by drugs inducing autophagy independently of mTOR activation PubMed:30061532

Appears in Networks:

p(FPLX:AKT) regulates act(p(HGNC:MTOR)) View Subject | View Object

In particular, DISC1 acts by blocking KIAA1212, an Akt-binding partner, which directly interacts with Akt and strengthens the activation of this kinase, which represents a major mediator of the mTOR pathway. PubMed:30061532

Appears in Networks:

complex(p(HGNC:CCDC88A), p(HGNC:DISC1)) decreases act(p(HGNC:MTOR)) View Subject | View Object

This decreases Akt activity, which in turn dampens mTOR signaling PubMed:30061532

Appears in Networks:

p(HGNC:NRG1) association act(p(HGNC:MTOR)) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

Appears in Networks:

act(g(HGNC:DISC1)) association act(p(HGNC:MTOR)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

Appears in Networks:

act(g(HGNC:DPYSL2)) association act(p(HGNC:MTOR)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

Appears in Networks:

act(g(HGNC:NRG1)) association act(p(HGNC:MTOR)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

Appears in Networks:

p(HGNC:DISC1, var("?")) increases act(p(HGNC:MTOR)) View Subject | View Object

Therefore, disruption of DISC1 activity, due to genetic rearrangements (i.e., balanced (1;11) (q42;q14) chromosomal translocation) or missense mutations, produces schizophrenic-like behavior, which is bound to enhanced Akt activity, over-activation of mTOR signaling, and depressed autophagy PubMed:30061532

Appears in Networks:

act(p(HGNC:DRD1)) increases act(p(HGNC:MTOR)) View Subject | View Object

This is key, because abnormal stimulation of D1R and subsequent signaling cascades were recently shown to produce an over-activation of mTOR and inhibition of the autophagy machinery PubMed:30061532

Appears in Networks:

act(p(HGNC:DRD1)) increases act(p(HGNC:MTOR)) View Subject | View Object

Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532

Appears in Networks:

p(HGNC:MAP6) association act(p(HGNC:MTOR)) View Subject | View Object

The biological implication behind an impairment of microtubule dynamics is confirmed in post-mortem schizophrenic brain samples, as well as in mouse models of schizophrenia, where mTOR-dependent autophagy dysfunction is accompanied by an altered gene expression and protein levels of the microtubule-associated protein 6 (MAP6) PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Schizophrenia

path(MESH:"Neurodegenerative Diseases") positiveCorrelation act(p(HGNC:MTOR)) View Subject | View Object

Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) association act(p(HGNC:MTOR)) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation act(p(HGNC:MTOR)) View Subject | View Object

Remarkably, the identification of rare genetic variants of ULK1 in a cohort of schizophrenic patients by means of exome sequence analysis strengthens the idea of a key role of both disrupted mTOR signaling and autophagy in the pathophysiology and susceptibility to schizophrenia PubMed:30061532

Appears in Networks:

a(GO:"actin cytoskeleton") association p(HGNC:MTOR) View Subject | View Object

Likewise, mechanistic target of rapamycin (Mtor), which has been linked to cellular regulation, protein translation, autophagy, and the actin cytoskeleton (43–45), was also found to be regulated by ADNP and NAP PubMed:30106381

Appears in Networks:

a(PUBCHEM:9832404) regulates p(HGNC:MTOR) View Subject | View Object

Likewise, mechanistic target of rapamycin (Mtor), which has been linked to cellular regulation, protein translation, autophagy, and the actin cytoskeleton (43–45), was also found to be regulated by ADNP and NAP PubMed:30106381

Appears in Networks:

bp(GO:autophagy) association p(HGNC:MTOR) View Subject | View Object

Likewise, mechanistic target of rapamycin (Mtor), which has been linked to cellular regulation, protein translation, autophagy, and the actin cytoskeleton (43–45), was also found to be regulated by ADNP and NAP PubMed:30106381

Appears in Networks:

bp(GO:translation) association p(HGNC:MTOR) View Subject | View Object

Likewise, mechanistic target of rapamycin (Mtor), which has been linked to cellular regulation, protein translation, autophagy, and the actin cytoskeleton (43–45), was also found to be regulated by ADNP and NAP PubMed:30106381

Appears in Networks:

p(HGNC:ADNP) regulates p(HGNC:MTOR) View Subject | View Object

Likewise, mechanistic target of rapamycin (Mtor), which has been linked to cellular regulation, protein translation, autophagy, and the actin cytoskeleton (43–45), was also found to be regulated by ADNP and NAP PubMed:30106381

Appears in Networks:

Out-Edges 24

p(HGNC:MTOR) positiveCorrelation p(HGNC:MAPT, pmod(Ph)) 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

Appears in Networks:

p(HGNC:MTOR) negativeCorrelation bp(GO:autophagy) 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

Appears in Networks:

p(HGNC:MTOR) regulates bp(GO:autophagy) View Subject | View Object

Induction of autophagy is generally controlled by the mTOR kinase (mammalian Target of Rapamycin), which is regulated by growth factors (especially insulin) and nutrient levels. PubMed:22908190

Appears in Networks:

act(p(HGNC:MTOR)) regulates deg(p(MESH:Proteins, pmod(HBP:misfolded))) View Subject | View Object

Remarkably, further investigation on the autophagy pathway revealed that all these misfolded proteins are autophagy substrates depending on mTOR activity PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) negativeCorrelation bp(GO:autophagy) View Subject | View Object

Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) decreases bp(GO:autophagy) 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

Appears in Networks:

p(HGNC:MTOR) decreases bp(GO:autophagy) View Subject | View Object

The biological implication behind an impairment of microtubule dynamics is confirmed in post-mortem schizophrenic brain samples, as well as in mouse models of schizophrenia, where mTOR-dependent autophagy dysfunction is accompanied by an altered gene expression and protein levels of the microtubule-associated protein 6 (MAP6) PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Schizophrenia

act(p(HGNC:MTOR)) positiveCorrelation path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) increases a(CHEBI:"amyloid-beta") View Subject | View Object

For instance, an increased mTOR activity correlates with accumulation of Abeta and hyperphosphorylated tau in AD brains PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

act(p(HGNC:MTOR)) increases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

For instance, an increased mTOR activity correlates with accumulation of Abeta and hyperphosphorylated tau in AD brains PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

act(p(HGNC:MTOR)) increases path(MESH:"Alzheimer Disease") View Subject | View Object

On the other hand, some evidence indicates that suppressing mTOR activity ameliorates AD cognitive defects by decreasing Abeta and tau pathology PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) increases a(HBP:"Tau aggregates") View Subject | View Object

On the other hand, some evidence indicates that suppressing mTOR activity ameliorates AD cognitive defects by decreasing Abeta and tau pathology PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) decreases bp(GO:cognition) View Subject | View Object

On the other hand, some evidence indicates that suppressing mTOR activity ameliorates AD cognitive defects by decreasing Abeta and tau pathology PubMed:30061532

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:MTOR)) association act(g(HGNC:DISC1)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) association act(g(HGNC:NRG1)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) association act(g(HGNC:DPYSL2)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) increases 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

Appears in Networks:

act(p(HGNC:MTOR)) association p(HGNC:MAP6) View Subject | View Object

The biological implication behind an impairment of microtubule dynamics is confirmed in post-mortem schizophrenic brain samples, as well as in mouse models of schizophrenia, where mTOR-dependent autophagy dysfunction is accompanied by an altered gene expression and protein levels of the microtubule-associated protein 6 (MAP6) PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Schizophrenia

act(p(HGNC:MTOR)) association p(HGNC:NRG1) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) association path(MESH:Schizophrenia) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Remarkably, the identification of rare genetic variants of ULK1 in a cohort of schizophrenic patients by means of exome sequence analysis strengthens the idea of a key role of both disrupted mTOR signaling and autophagy in the pathophysiology and susceptibility to schizophrenia PubMed:30061532

Appears in Networks:

p(HGNC:MTOR) association bp(GO:translation) View Subject | View Object

Likewise, mechanistic target of rapamycin (Mtor), which has been linked to cellular regulation, protein translation, autophagy, and the actin cytoskeleton (43–45), was also found to be regulated by ADNP and NAP PubMed:30106381

Appears in Networks:

p(HGNC:MTOR) association bp(GO:autophagy) View Subject | View Object

Likewise, mechanistic target of rapamycin (Mtor), which has been linked to cellular regulation, protein translation, autophagy, and the actin cytoskeleton (43–45), was also found to be regulated by ADNP and NAP PubMed:30106381

Appears in Networks:

p(HGNC:MTOR) association a(GO:"actin cytoskeleton") View Subject | View Object

Likewise, mechanistic target of rapamycin (Mtor), which has been linked to cellular regulation, protein translation, autophagy, and the actin cytoskeleton (43–45), was also found to be regulated by ADNP and NAP PubMed:30106381

Appears in Networks:

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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.