p(HGNC:MTOR)
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
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
For instance, adenosine monophosphate- activated protein kinase (AMPK) phosphorylates ULK1 and inactivates mTOR through the raptor and tuberous sclerosis complex (TSC2). PubMed:29758300
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
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
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
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
In contrast, chlorpromazine, which is a typical antipsychotic agent, induces autophagy by inhibiting the Akt/mTOR pathway PubMed:30061532
In fact, lithium is able to delay METH-induced sensitization, while being a powerful treatment in schizophrenia PubMed:30061532
Again, rapamycin and rapalogs protect against toxicity produced by a number of misfolded proteins encompassing alpha synuclein, TDP43, and hyperphosphorylated tau PubMed:30061532
Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532
Again, rapamycin and rapalogs protect against toxicity produced by a number of misfolded proteins encompassing alpha synuclein, TDP43, and hyperphosphorylated tau PubMed:30061532
Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532
The relevance of autophagy for sustaining these mTOR-induced effects is confirmed by drugs inducing autophagy independently of mTOR activation PubMed:30061532
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
This decreases Akt activity, which in turn dampens mTOR signaling PubMed:30061532
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
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
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
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
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
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
Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532
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
Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532
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
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
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
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
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
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
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
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
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
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
Remarkably, further investigation on the autophagy pathway revealed that all these misfolded proteins are autophagy substrates depending on mTOR activity PubMed:30061532
Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532
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
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
Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532
For instance, an increased mTOR activity correlates with accumulation of Abeta and hyperphosphorylated tau in AD brains PubMed:30061532
For instance, an increased mTOR activity correlates with accumulation of Abeta and hyperphosphorylated tau in AD brains PubMed:30061532
On the other hand, some evidence indicates that suppressing mTOR activity ameliorates AD cognitive defects by decreasing Abeta and tau pathology PubMed:30061532
On the other hand, some evidence indicates that suppressing mTOR activity ameliorates AD cognitive defects by decreasing Abeta and tau pathology PubMed:30061532
On the other hand, some evidence indicates that suppressing mTOR activity ameliorates AD cognitive defects by decreasing Abeta and tau pathology PubMed:30061532
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
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
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
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
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
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
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
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
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
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
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
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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.