Nicastrin Palmitoylation and Biology of Gamma Secretase

Gopal Thinakaran, PhD
University of Chicago (Chicago, IL)
Year Awarded:
2004
Grant Duration:
April 1, 2004 to March 31, 2006
Disease:
Alzheimer's Disease
Award Amount:
$300,000
Grant Reference ID:
A2004104
Award Type:
Standard
Award Region:
US Midwestern

Nicastrin Palmitoylation and Biology of Gamma Secretase

Details


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).

Publications

Vetrivel, K.S., Cheng, H., Lin, W., Sakurai, T., Li, T., Nukina, N., Wong, P.C., Xu, H. and Thinakaran, G. (2004) Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. J Biol Chem. 279(43):44945-44954.  

Thinakaran, G. and Parent, A.T. (2004) Identification of the Role of Presenilins beyond Alzheimer's disease. Pharmacol. Res. 50:411-418.  

Vetrivel KS, Zhang YW, Xu H and Thinakaran G: Pathological and physiological functions of presenilins. Mol. Neurodegener. 1:4, 2006.  

Vetrivel KS and Thinakaran G: Amyloidogenic processing of Beta-amyloid precursor protein in intracellular compartments. Neurology 66(2 Suppl 1):S69-73, 2006.  

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