Regulation of amyloid precursor protein expression and metabolism by Hu proteins

The β-amyloid peptide that accumulates in Alzheimer’s disease (AD) brain, derives from proteolytic processing of the amyloid precursor protein (APP). APP is present in three main isoforms derived by alternative splicing, the ubiquitously expressed APP770 and APP751 and the neuronally enriched and less amyloidogenic APP695. Our preliminary studies suggest that neuronal RNA-binding Hu proteins are possibly involved in APP alternative splicing generating APP695. Interestingly, neuronal Hu proteins have been implicated in cognitive processes and their levels, as well as those of APP695, are reduced in AD brains. This proposal aims at characterizing the role of Hu proteins in the post-transcriptional regulation of APP expression, as well as their impact on APP proteolytic processing. We believe that the present study will enhance our understanding concerning the regulation of APP expression and metabolism and provide insight for the development of novel therapeutic targets for AD.

This project was evaluated and funded as part of the Foundation’s effort to support research teams with all their members being under 40 years old.