CIDeRplusGeneral Information:
| Id: | 6,542 |
| Diseases: |
Alzheimer disease
- [OMIM]
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| Mammalia | |
| review | |
| Reference: | Cai Z et al.(2012) Roles of AMP-activated protein kinase in Alzheimers disease Neuromolecular Med. 14: 1-14 [PMID: 22367557] |
Interaction Information:
| Comment | AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis and a central player in glucose and lipid metabolism, is potentially implicated in the pathogenesis of Alzheimer’s disease (AD). AMPK activity decreases in AD brain, indicating decreased mitochondrial biogenesis and function. |
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Formal Description Interaction-ID: 62207 |
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| Comment | The roles of AMPK in the pathogenesis of AD include beta-amyloid protein (Abeta) generation and tau phosphorylation. AMPK is a physiological tau kinase and can increase the phosphorylation of tau at Ser-262. AMPK can also directly phosphorylate tau at Thr-231 and Ser-396/404. In particular, AMPK may regulate Abeta generation through modulating neuronal cholesterol and sphingomyelin levels and through regulating APP distribution in the lipid rafts. Accumulating studies indicate that AMPK is a neuroprotective factor against metabolic stress, implicating a significant role in the prevention of AD pathology. Accordingly, AMPK plays an important role in the pathogenesis of AD and is a potential therapeutic target for AD. Research studies also demonstrated that the activation of AMPK has non-neuroprotective property and could lead to detrimental outcomes. |
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Formal Description Interaction-ID: 63306 |
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| Comment | AMPK is activated by phosphorylation of Thr-172 by LKB1 complex in response to increase in the AMP/ATP ratio and by calmodulin-dependent protein kinase kinase-beta in response to elevated Ca 2+ levels, which contributes to regulating Abeta generation. |
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Formal Description Interaction-ID: 63307 |
gene/protein increases_phosphorylation of complex/PPI AMPK |
| Comment | AMPK activation decreases mTOR signaling activity to facilitate autophagy and promotes lysosomal degradation of Abeta. However, AMPK activation has non-neuroprotective property and may lead to detrimental outcomes, including Abeta generation and tau phosphorylation. |
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Formal Description Interaction-ID: 63308 |
complex/PPI AMPK decreases_activity of process |
| Comment | AMPK is activated by phosphorylation of Thr-172 by LKB1 complex in response to increase in the AMP/ATP ratio and by calmodulin-dependent protein kinase kinase-beta in response to elevated Ca 2+ levels, which contributes to regulating Abeta generation. |
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Formal Description Interaction-ID: 63436 |
gene/protein increases_phosphorylation of complex/PPI AMPK |
| Comment | AMPK is activated by phosphorylation of Thr-172 by LKB1 complex in response to increase in the AMP/ATP ratio and by calmodulin-dependent protein kinase kinase-beta in response to elevated Ca 2+ levels, which contributes to regulating Abeta generation. |
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Formal Description Interaction-ID: 63437 |
gene/protein increases_activity of complex/PPI AMPK |
| Comment | AMPK is activated by phosphorylation of Thr-172 by LKB1 complex in response to increase in the AMP/ATP ratio and by calmodulin-dependent protein kinase kinase-beta in response to elevated Ca 2+ levels, which contributes to regulating Abeta generation. |
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Formal Description Interaction-ID: 63438 |
gene/protein increases_activity of complex/PPI AMPK |
| Comment | AMPK activation decreases mTOR signaling activity to facilitate autophagy and promotes lysosomal degradation of Abeta. However, AMPK activation has non-neuroprotective property and may lead to detrimental outcomes, including Abeta generation and tau phosphorylation. |
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Formal Description Interaction-ID: 63439 |
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| Comment | AMPK activation decreases mTOR signaling activity to facilitate autophagy and promotes lysosomal degradation of Abeta. However, AMPK activation has non-neuroprotective property and may lead to detrimental outcomes, including Abeta generation and tau phosphorylation. Therefore, it is still unclear whether AMPK could serve a potential therapeutic target for AD. |
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Formal Description Interaction-ID: 63440 |
complex/PPI AMPK decreases_quantity of gene/protein |
| Comment | AMPK exists as a heterotrimeric complex composed of alpha-catalytic subunit and beta- and gamma-regulatory subunits. The alpha-,beta-, and gamma-subunits can also be found in different isoforms: gamma-1, gamma-2, or gamma-3 isoform for gamma-subunit; beta-1or beta-2 isoform for beta-subunit; and alpha-1or alpha-2 isoform for alpha-subunit. The alpha-subunits contain the Thr172 residue that must be phosphorylated by upstream kinases for activity and an autoinhibitory sequence domain that inhibits the activity of the kinase domain. The C-terminal domain of alpha-subunits is required for binding the beta- and gamma-subunits. Research evidence also revealed that the AMPK alpha-2 contributes to the deleterious effects of AMPK activation in stroke. Overactivation of AMPK alpha-1 potentiates striatal neurodegeneration in Huntington’s disease. |
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Formal Description Interaction-ID: 63557 |
gene/protein PRKAA is_part_of complex/PPI AMPK |
| Comment | AMPK exists as a heterotrimeric complex composed of alpha-catalytic subunit and beta- and gamma-regulatory subunits. The alpha-,beta-, and gamma-subunits can also be found in different isoforms: gamma-1, gamma-2, or gamma-3 isoform for gamma-subunit; beta-1or beta-2 isoform for beta-subunit; and alpha-1or alpha-2 isoform for alpha-subunit. The beta-subunits contain central glycogen-binding domains and C-terminal domain that is required for binding the alpha- and gamma-subunits. In both the inactive and active conformations, the beta-subunit acts as a scaffold that binds alpha- and gamma-subunits. |
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Formal Description Interaction-ID: 63562 |
gene/protein PRKAB is_part_of complex/PPI AMPK |
| Comment | AMPK exists as a heterotrimeric complex composed of alpha-catalytic subunit and beta- and gamma-regulatory subunits. The alpha-,beta-, and gamma-subunits can also be found in different isoforms: gamma-1, gamma-2, or gamma-3 isoform for gamma-subunit; beta-1or beta-2 isoform for beta-subunit; and alpha-1 or alpha-2 isoform for alpha-subunit. The gamma-subunit of AMPK undergoes a conformational change to expose the active site (Thr-172) on the alpha-subunit. The gamma-subunit isoforms have variable N-terminal domains and four conserved cystathionine beta-synthase motifs (CBS1‚Äď4) that bind AMP or ATP. |
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Formal Description Interaction-ID: 63563 |
gene/protein PRKAG is_part_of complex/PPI AMPK |
| Comment | AMPK subunits are constantly expressed in neurons and thus can be functionally activated. AMPK regulates energy balance at both the cellular and whole-body levels. |
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Formal Description Interaction-ID: 63569 |
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| Comment | AMPK subunits are constantly expressed in neurons and thus can be functionally activated. AMPK regulates energy balance at both the cellular and whole-body levels. |
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Formal Description Interaction-ID: 63571 |
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| Comment | AMPK subunits are constantly expressed in neurons and thus can be functionally activated. AMPK regulates energy balance at both the cellular and whole-body levels. |
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Formal Description Interaction-ID: 63572 |
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| Comment | AMPK subunits are constantly expressed in neurons and thus can be functionally activated. AMPK regulates energy balance at both the cellular and whole-body levels. It is switched on in response to metabolic stresses and modulated by hormones and cytokines affecting whole-body energy balance. Once activated, AMPK switches on catabolic pathways that generate ATP. |
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Formal Description Interaction-ID: 63574 |
complex/PPI AMPK affects_activity of process |
| Comment | Metformin, the first-line drug of choice for the treatment of type 2 diabetes, is an activator (maybe through LKB1) of AMPK and many of its effects are probably driven through AMPK pathway. |
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Formal Description Interaction-ID: 63578 |
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| Drugbank entries | Show/Hide entries for Metformin |
| Comment | Generation of Abeta peptides, the amyloidogenic pathway, begins with beta-secretase-mediated extracellular cleavage between the Met671 and Asp672 residues of APP, which creates a soluble extracellular fragment (sAPPbeta) and a cell membrane-bound fragment (C99). Subsequent to BACE cleavage, the 12 kD C-terminal fragment (C99) can then be further cleaved by gamma-secretase complex within the hydrophobic transmembrane domain at either Val711 or Ile713, releasing the intracellular domain of APP and producing Abeta. |
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Formal Description Interaction-ID: 63581 |
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| Drugbank entries | Show/Hide entries for BACE1 or APP |
| Comment | Generation of Abeta peptides, the amyloidogenic pathway, begins with beta-secretase-mediated extracellular cleavage between the Met671 and Asp672 residues of APP, which creates a soluble extracellular fragment (sAPPbeta) and a cell membrane-bound fragment (C99). Subsequent to BACE cleavage, the 12 kD C-terminal fragment (C99) can then be further cleaved by gamma-secretase complex within the hydrophobic transmembrane domain at either Val711 or Ile713, releasing the intracellular domain of APP and producing Abeta. |
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Formal Description Interaction-ID: 63587 |
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| Drugbank entries | Show/Hide entries for BACE1 |
| Comment | Generation of Abeta peptides, the amyloidogenic pathway, begins with beta-secretase-mediated extracellular cleavage between the Met671 and Asp672 residues of APP, which creates a soluble extracellular fragment (sAPPbeta) and a cell membrane-bound fragment (C99). Subsequent to BACE cleavage, the 12 kD C-terminal fragment (C99) can then be further cleaved by gamma-secretase complex within the hydrophobic transmembrane domain at either Val711 or Ile713, releasing the intracellular domain of APP and producing Abeta. |
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Formal Description Interaction-ID: 63588 |
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| Drugbank entries | Show/Hide entries for BACE1 |
| Comment | In the non-amyloidogenic pathway, APP may be processed by alpha-secretase, generating sAPP-alpha and preventing Abeta generation. |
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Formal Description Interaction-ID: 63591 |
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| Drugbank entries | Show/Hide entries for APP |
| Comment | In the non-amyloidogenic pathway, APP may be processed by alpha-secretase, generating sAPP-alpha and preventing Abeta generation. |
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Formal Description Interaction-ID: 63592 |
gene/protein Alpha-secretase increases_quantity of gene/protein |
| Comment | Research studies showed that direct stimulation of AMPK with AICAR inhibits tau phosphorylation and conversely, an inhibition with compound C, increases tau phosphorylation, implicating that AMPK is a key regulator of tau phosphorylation. |
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Formal Description Interaction-ID: 63593 |
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| Drugbank entries | Show/Hide entries for AICAR |
| Comment | Research studies showed that direct stimulation of AMPK with AICAR inhibits tau phosphorylation and conversely, an inhibition with compound C, increases tau phosphorylation, implicating that AMPK is a key regulator of tau phosphorylation. |
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Formal Description Interaction-ID: 63594 |
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| Comment | Research studies showed that direct stimulation of AMPK with AICAR inhibits tau phosphorylation and conversely, an inhibition with compound C, increases tau phosphorylation, implicating that AMPK is a key regulator of tau phosphorylation. |
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Formal Description Interaction-ID: 63597 |
drug/chemical compound Compound C decreases_activity of complex/PPI AMPK |
| Comment | Research studies showed that direct stimulation of AMPK with AICAR inhibits tau phosphorylation and conversely, an inhibition with compound C, increases tau phosphorylation, implicating that AMPK is a key regulator of tau phosphorylation. |
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Formal Description Interaction-ID: 63598 |
drug/chemical compound Compound C increases_phosphorylation of gene/protein |
| Comment | AMPK itself phosphorylates tau at Ser262 and Ser396 through altering microtubule binding of tau. AMPK plays a role in the pathophysiological phosphorylation of tau via the NMDA receptor upstream of AMPK in a CaMKKbeta-mediated activation pathway. Recent research found that AMPK can directly phosphorylate tau at Thr-231 and Ser-396/404 show that activated AMPK (p-AMPK) is abnormally accumulated in cerebral neurons in 3R(3 repeat tau) and 4R (4 repeat tau) tauopathies, including AD. In AD brains, p-AMPK accumulation decorated neuropil threads and dystrophic neurites surrounding amyloid plaques and appeared in more than 90% of neurons bearing pretangles and tangles. p-AMPK was not found in purified PHFs, indicating that p-AMPK did not co-aggregate with tau in tangles. These data suggest that AMPK activation preceded tau accumulation. |
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Formal Description Interaction-ID: 63599 |
complex/PPI AMPK increases_phosphorylation of gene/protein |
| Comment | AMPK itself phosphorylates tau at Ser262 and Ser396 through altering microtubule binding of tau. AMPK plays a role in the pathophysiological phosphorylation of tau via the NMDA receptor upstream of AMPK in a CaMKKbeta-mediated activation pathway. Recent research found that AMPK can directly phosphorylate tau at Thr-231 and Ser-396/404 show that activated AMPK (p-AMPK) is abnormally accumulated in cerebral neurons in 3R(3 repeat tau) and 4R (4 repeat tau) tauopathies, including AD. In AD brains, p-AMPK accumulation decorated neuropil threads and dystrophic neurites surrounding amyloid plaques and appeared in more than 90% of neurons bearing pretangles and tangles. p-AMPK was not found in purified PHFs, indicating that p-AMPK did not co-aggregate with tau in tangles. These data suggest that AMPK activation preceded tau accumulation. |
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Formal Description Interaction-ID: 63604 |
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| Comment | AMPK itself phosphorylates tau at Ser262 and Ser396 through altering microtubule binding of tau. AMPK plays a role in the pathophysiological phosphorylation of tau via the NMDA receptor upstream of AMPK in a CaMKKbeta-mediated activation pathway. Recent research found that AMPK can directly phosphorylate tau at Thr-231 and Ser-396/404 show that activated AMPK (p-AMPK) is abnormally accumulated in cerebral neurons in 3R(3 repeat tau) and 4R (4 repeat tau) tauopathies, including AD. In AD brains, p-AMPK accumulation decorated neuropil threads and dystrophic neurites surrounding amyloid plaques and appeared in more than 90% of neurons bearing pretangles and tangles. p-AMPK was not found in purified PHFs, indicating that p-AMPK did not co-aggregate with tau in tangles. These data suggest that AMPK activation preceded tau accumulation. |
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Formal Description Interaction-ID: 63605 |
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| Comment | Autophagy is a key clearance pathway involved in the removal of aberrant aggregates of Abeta and tau proteins. Induction of autophagy enhances the clearance of both soluble and aggregated forms of Abeta and tau proteins in vivo and vitro. Autophagy is constitutively active and highly efficient in healthy neurons and the autophagy pathology observed in AD most likely arises from impaired clearance of autophagic vacuoles rather than strong autophagy induction alone. A chronic deterioration of the neuronal autophagy-lysosomal system is likely to be a key event in transitioning from normal brain aging to pathological aging leading to Alzheimer’s neurodegeneration. An improper clearance of proteins in AD may either result from a compromise in the autophagy-lysosomal degradation pathway or induce alterations in this pathway and may result in neuron dysfunction and neuron loss. |
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Formal Description Interaction-ID: 63606 |
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| Comment | As a central controller, overwhelming data demonstrated that mTOR plays a critical role in AD pathogenesis and decreased mTOR pathway induces Abeta production and accumulation of tau. In addition, the upstream and downstream components of mTOR signaling pathway are involved in a wide variety of AD pathogenesis. Rapamycin, an inhibitor of mTOR, rescued learning and memory deficits in a mouse model of AD and reduced Abeta and tau pathology. Collectively, the mTOR pathway is a critical regulator of Abeta and tau protein through controlling autophagy pathway. |
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Formal Description Interaction-ID: 63607 |
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| Comment | As a central controller, overwhelming data demonstrated that mTOR plays a critical role in AD pathogenesis and decreased mTOR pathway induces Abeta production and accumulation of tau. In addition, the upstream and downstream components of mTOR signaling pathway are involved in a wide variety of AD pathogenesis. Rapamycin, an inhibitor of mTOR, rescued learning and memory deficits in a mouse model of AD and reduced Abeta and tau pathology. Collectively, the mTOR pathway is a critical regulator of Abeta and tau protein through controlling autophagy pathway. |
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Formal Description Interaction-ID: 63608 |
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| Comment | As a central controller, overwhelming data demonstrated that mTOR plays a critical role in AD pathogenesis and decreased mTOR pathway induces Abeta production and accumulation of tau. In addition, the upstream and downstream components of mTOR signaling pathway are involved in a wide variety of AD pathogenesis. Rapamycin, an inhibitor of mTOR, rescued learning and memory deficits in a mouse model of AD and reduced Abeta and tau pathology. Collectively, the mTOR pathway is a critical regulator of Abeta and tau protein through controlling autophagy pathway. |
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Formal Description Interaction-ID: 63609 |
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| Comment | As a central controller, overwhelming data demonstrated that mTOR plays a critical role in AD pathogenesis and decreased mTOR pathway induces Abeta production and accumulation of tau. In addition, the upstream and downstream components of mTOR signaling pathway are involved in a wide variety of AD pathogenesis. Rapamycin, an inhibitor of mTOR, rescued learning and memory deficits in a mouse model of AD and reduced Abeta and tau pathology. Collectively, the mTOR pathway is a critical regulator of Abeta and tau protein through controlling autophagy pathway. |
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Formal Description Interaction-ID: 63610 |
drug/chemical compound increases_activity of process |
| Comment | As a central controller, overwhelming data demonstrated that mTOR plays a critical role in AD pathogenesis and decreased mTOR pathway induces Abeta production and accumulation of tau. In addition, the upstream and downstream components of mTOR signaling pathway are involved in a wide variety of AD pathogenesis. Rapamycin, an inhibitor of mTOR, rescued learning and memory deficits in a mouse model of AD and reduced Abeta and tau pathology. Collectively, the mTOR pathway is a critical regulator of Abeta and tau protein through controlling autophagy pathway. |
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Formal Description Interaction-ID: 63611 |
drug/chemical compound decreases_activity of gene/protein |
| Comment | As a central controller, overwhelming data demonstrated that mTOR plays a critical role in AD pathogenesis and decreased mTOR pathway induces Abeta production and accumulation of tau. In addition, the upstream and downstream components of mTOR signaling pathway are involved in a wide variety of AD pathogenesis. Rapamycin, an inhibitor of mTOR, rescued learning and memory deficits in a mouse model of AD and reduced Abeta and tau pathology. Collectively, the mTOR pathway is a critical regulator of Abeta and tau protein through controlling autophagy pathway. |
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Formal Description Interaction-ID: 63612 |
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| Comment | Autophagy is promoted by AMPK through direct phosphorylation of ULK1, whereas autophagy is inhibited by mTOR, a central cell growth regulator that integrates growth factor and nutrient signals. |
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Formal Description Interaction-ID: 63613 |
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| Comment | Autophagy is promoted by AMPK through direct phosphorylation of ULK1, whereas autophagy is inhibited by mTOR, a central cell growth regulator that integrates growth factor and nutrient signals. |
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Formal Description Interaction-ID: 63614 |
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| Comment | Autophagy is promoted by AMPK through direct phosphorylation of ULK1, whereas autophagy is inhibited by mTOR, a central cell growth regulator that integrates growth factor and nutrient signals. |
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Formal Description Interaction-ID: 63615 |
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| Comment | Autophagy is promoted by AMPK through direct phosphorylation of ULK1, whereas autophagy is inhibited by mTOR, a central cell growth regulator that integrates growth factor and nutrient signals. |
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Formal Description Interaction-ID: 63616 |
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| Drugbank entries | Show/Hide entries for MTOR |
| Comment | The increase in cytosolic Ca2+ can induce autophagy by inhibition of mTOR through the CaMKKbeta-mediated activation of AMPK. |
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Formal Description Interaction-ID: 63622 |
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| Comment | The increase in cytosolic Ca2+ can induce autophagy by inhibition of mTOR through the CaMKKbeta-mediated activation of AMPK. |
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Formal Description Interaction-ID: 63626 |
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| Comment | The increase in cytosolic Ca2+ can induce autophagy by inhibition of mTOR through the CaMKKbeta-mediated activation of AMPK. |
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Formal Description Interaction-ID: 63627 |
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| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63631 |
drug/chemical compound increases_activity of complex/PPI AMPK |
| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63755 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63756 |
drug/chemical compound increases_phosphorylation of complex/PPI AMPK |
| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63757 |
drug/chemical compound decreases_activity of gene/protein |
| Drugbank entries | Show/Hide entries for Resveratrol or MTOR |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63758 |
drug/chemical compound decreases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63759 |
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| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63760 |
drug/chemical compound increases_activity of gene/protein |
| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63761 |
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| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63762 |
drug/chemical compound RSVA314 increases_activity of complex/PPI AMPK |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63763 |
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| Drugbank entries | Show/Hide entries for MTOR |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63764 |
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| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63765 |
drug/chemical compound RSVA314 decreases_quantity of gene/protein |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63766 |
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| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63767 |
drug/chemical compound RSVA405 increases_activity of complex/PPI AMPK |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63768 |
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| Drugbank entries | Show/Hide entries for MTOR |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63769 |
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| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63770 |
drug/chemical compound RSVA405 decreases_quantity of gene/protein |
| Comment | Resveratrol activates AMPK by increasing intracellular Ca2+ levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKbeta and thus lowers Abeta levels through inhibiting mTOR to induce autophagy and then promoting intracellular degradation of Abeta by the lysosomal system in vitro. Two of resveratrol analogues, RSVA314 and RSVA405, share with resveratrol the same mechanism of action: facilitating CaMKKbeta-dependent activation of AMPK, inhibiting mTOR, and promoting autophagy and lysosomal degradation of Abeta. |
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Formal Description Interaction-ID: 63771 |
process decreases_quantity of gene/protein |
| Comment | AMPK activation decreases mTOR signaling activity to facilitate autophagy and promotes lysosomal degradation of Abeta. However, AMPK activation has non-neuroprotective property and may lead to detrimental outcomes, including Abeta generation and tau phosphorylation. |
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Formal Description Interaction-ID: 63775 |
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| Drugbank entries | Show/Hide entries for MTOR |
| Comment | AMPK activation decreases mTOR signaling activity to facilitate autophagy and promotes lysosomal degradation of Abeta. However, AMPK activation has non-neuroprotective property and may lead to detrimental outcomes, including Abeta generation and tau phosphorylation. |
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Formal Description Interaction-ID: 63776 |
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| Drugbank entries | Show/Hide entries for MTOR |
| Comment | If AMPK is abnormally activated, it can directly phosphorylate tau at Thr-231 and Ser-396/404 in tangle- and pretangle-bearing neurons in AD and other tauopathies. Therefore, AMPK could be either a foe or a friend in Abeta generation and tau aggregation. |
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Formal Description Interaction-ID: 63820 |
complex/PPI AMPK increases_activity of disease Tauopathy |
| Comment | Melatonin potentiates the neuroprotective properties of resveratrol against Abeta-induced neurodegeneration by modulating AMPK pathways. |
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Formal Description Interaction-ID: 63857 |
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| Drugbank entries | Show/Hide entries for Melatonin or Resveratrol |