Abstract
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
Current Signal Transduction Therapy
Title: Presenilin and γ -Secretase Activity: A Viable Therapeutic Target for Alzheimers Disease?
Volume: 5 Issue: 2
Author(s): Run Yan and Justin V. McCarthy
Affiliation:
Keywords: Alzheimer's disease, Amyloid-beta (Aβ), gamma-secretase, presenilin, regulated intramembrane proteolysis, posttranslational modification
Abstract: 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.
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Cite this article as:
Yan Run and V. McCarthy Justin, Presenilin and γ -Secretase Activity: A Viable Therapeutic Target for Alzheimers Disease?, Current Signal Transduction Therapy 2010; 5 (2) . https://dx.doi.org/10.2174/157436210791112217
DOI https://dx.doi.org/10.2174/157436210791112217 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
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