Presenilins and -Secretase: Structure, Function, and Role in Alzheimer Disease
Open Access
- 8 November 2011
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Cold Spring Harbor Perspectives in Medicine
- Vol. 2 (1), a006304
- https://doi.org/10.1101/cshperspect.a006304
Abstract
Presenilins were first discovered as sites of missense mutations responsible for early-onset Alzheimer disease (AD). The encoded multipass membrane proteins were subsequently found to be the catalytic components of γ-secretases, membrane-embedded aspartyl protease complexes responsible for generating the carboxyl terminus of the amyloid β-protein (Aβ) from the amyloid protein precursor (APP). The protease complex also cleaves a variety of other type I integral membrane proteins, most notably the Notch receptor, signaling from which is involved in many cell differentiation events. Although γ-secretase is a top target for developing disease-modifying AD therapeutics, interference with Notch signaling should be avoided. Compounds that alter Aβ production by γ-secretase without affecting Notch proteolysis and signaling have been identified and are currently at various stages in the drug development pipeline.This publication has 163 references indexed in Scilit:
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