Home
Resources
Publications
Novel Synthetic Small-Molecule Activators of AMPK as Enhancers of Autophagy and amyloid-β Peptide Degradation

Novel Synthetic Small-Molecule Activators of AMPK as Enhancers of Autophagy and amyloid-β Peptide Degradation

Valérie Vingtdeux, Pallavi Chandakkar, Haitian Zhao, Cristina d'Abramo, Peter Davies, Philippe Marambaud

FASEB J. 2011 Jan;25(1):219-31.

PMID: 20852062

Abstract:

AMP-activated protein kinase (AMPK) is a metabolic sensor involved in intracellular energy metabolism through the control of several homeostatic mechanisms, which include autophagy and protein degradation. Recently, we reported that AMPK activation by resveratrol promotes autophagy-dependent degradation of the amyloid-β (Aβ) peptides, the core components of the cerebral senile plaques in Alzheimer's disease. To identify more potent enhancers of Aβ degradation, we screened a library of synthetic small molecules selected for their structural similarities with resveratrol. Here, we report the identification of a series of structurally related molecules, the RSVA series, which inhibited Aβ accumulation in cell lines nearly 40 times more potently than did resveratrol. Two of these molecules, RSVA314 and RSVA405, were further characterized and were found to facilitate CaMKKβ-dependent activation of AMPK, to inhibit mTOR (mammalian target of rapamycin), and to promote autophagy to increase Aβ degradation by the lysosomal system (apparent EC(50) ∼ 1 μM). This work identifies the RSVA compounds as promising lead molecules for the development of a new class of AMPK activating drugs controlling mTOR signaling, autophagy, and Aβ clearance.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP316130822-B	RSVA314		316130-82-2	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: