Machado-Joseph Disease
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Sample Annotated Edges 5

a(CHEBI:cilostazol) decreases p(HGNC:MAPT, pmod(HBP:HBP00007)) View Subject | View Object

Cilostazol improved cognition and reduced levels of Aβ42 and hyperphosphorylated tau following intra- cerebroventricular injection of Aβ25–35 into mice 162,163 . PubMed:30116051

bp(GO:aging) decreases a(CHEBI:"NAD(+)") View Subject | View Object

Activity of the deacetylase SIRT1 declines with age, partially owing to limited availability of its co fac- tor, nicotinamide 24,56,156 . PubMed:30116051

complex(p(HGNC:BCL2), p(HGNC:BECN1)) decreases bp(GO:macroautophagy) View Subject | View Object

Disruption of this Bcl-2–beclin 1 complex is an alternative approach for promoting autophagy, as achieved in mouse fibroblasts by the BH3 mimetic ABT-737 (REF.177) . PubMed:30116051

a(PUBCHEM:16240819) decreases bp(HP:Neurodegeneration) View Subject | View Object

An unusual approach to augmenting autophagosome formation is represented by the brain- penetrant autophagy enhancer 99 (AUTEN-99), which blocks myotubularin-related protein 14 (MTMR14, also known as Jumpy), a phosphatase that inhibits the phos- phoinositide 3-kinase (PI3K)-mediated generation of the autophagosome membrane (FIG. 3) . AUTEN-99 aug- mented autophagic flux in isolated neurons, increased markers of autophagy in mouse brain and slowed neuro- degeneration in D. melanogaster models of PD and HD 181 . PubMed:30116051


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