AlphaScreen HTS and live-cell bioluminescence resonance energy transfer (BRET) assays for identification of Tau-Fyn SH3 interaction inhibitors for Alzheimer disease.

ABSTRACT: Alzheimer disease (AD) is the most common neurodegenerative disease, and with Americans' increasing longevity, it is becoming an epidemic. There are currently no effective treatments for this disorder. Abnormalities of Tau track more closely with cognitive decline than the most studied therapeutic target in AD, amyloid-β, but the optimal strategy for targeting Tau has not yet been identified. On the basis of considerable preclinical data from AD models, we hypothesize that interactions between Tau and the Src-family tyrosine kinase, Fyn, are pathogenic in AD. Genetically reducing either Tau or Fyn is protective in AD mouse models, and a dominant negative fragment of Tau that alters Fyn localization is also protective. Here, we describe a new AlphaScreen assay and a live-cell bioluminescenc

SUBMITTER: Cochran JN 

PROVIDER: S-EPMC4318572 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature