Hsp70 ATPase Modulators as Therapeutics for Alzheimer's and other Neurodegenerative Diseases.

摘要: Neurodegenerative diseases caused by abnormal accumulation of the microtubule associated protein tau (MAPT, tau) are collectively called tauopathies. The most devastating related disorder is Alzheimer’s disease (AD). Molecular chaperones such as heat shock proteins (Hsp) have emerged critical regulators stability. Several studies from our group and others shown that chaperone network can be targeted for development therapeutic strategies AD other neurodegenerative diseases. Here we will discuss a recent paper current work laboratory where manipulated ATPase activity 70-kDa (Hsp70) to regulate turnover. A high-throughput screening assay revealed several compounds activated or inhibited Hsp70’s activity. Inhibitors dramatically rapidly reduced levels, whereas activators stabilized tau, both in cells brain tissue. Moreover, increased levels Hsp70 improved inhibitor efficacy, suggesting therapies aimed at inducing followed inhibition its may very effective strategy treat AD. These findings demonstrate modify pathologies