Presenilin and γ -Secretase Activity: A Viable Therapeutic Target for Alzheimers Disease?

Author(s): Run Yan, Justin V. McCarthy

Journal Name: Current Signal Transduction Therapy

Volume 5 , Issue 2 , 2010

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In this review, we discuss the γ-secretase protease complexes, which are responsible for the generation of amyloid-β peptides that constitutes the amyloid plaques of Alzheimers disease (AD). We begin with a brief review on the amyloid-β precursor protein (APP), its proteolytic cleavage and a brief discussion on the pathogenesis of AD. We then present the four major components of the γ-secretase complexes - presenilin, nicastrin, Aph-1, and Pen-2 and also introduce the importance of post-translational modification activity of the γ-secretase complexes. We then discuss the diversity of γ-secretase substrates and proposed biological functions. Next we review the current therapeutic strategies aimed at developing selective inhibitors of AD-associated γ-secretase activities. Finally, we present a discussion, which serves as a platform for further questions into the viability of γ-secretase as an AD therapeutic target.

Keywords: Alzheimer's disease, Amyloid-beta (Aβ), gamma-secretase, presenilin, regulated intramembrane proteolysis, posttranslational modification

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Article Details

Year: 2010
Page: [128 - 140]
Pages: 13
DOI: 10.2174/157436210791112217
Price: $65

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