Nicastrin Palmitoylation and Biology of Gamma Secretase

Project Summary

Recent research efforts have uncovered a common thread that connects the effects of mutations in the proteins termed Presenilin 1, Presenilin 2 and the amyloid precursor protein (APP). All three mutant proteins increase the production of toxic beta-amyloid peptide (Aß), which accumulates in the brains of individuals with Alzheimer's disease (AD). Dr. Thinakaran's research seeks to gain new information regarding the molecules that play an essential role in the production of Aß peptides. Presenilins and a few other proteins act together to generate Aß by the enzymatic cleavage of amyloid precursor protein. Recently, specialized microdomains in the cell surface, called lipid raft, were found to be involved in the production of Aß. A better understanding of the relationship between Presenilin and associated proteins and lipid rafts will shed more light on the mechanisms involved in Aß production, and perhaps, lead to new therapeutic interventions for Alzheimer's disease (AD).