RESEARCH ARTICLE


β- and γ-Secretases and Lipid Rafts



Wataru Araki*
Department of Demyelinating Disease and Aging National Institute of Neuroscience, NCNP Kodaira, Tokyo 187-8502 Japan.


© 2010 Wataru Araki

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, 4-1-1 Ogawamachi, Kodaira, Tokyo 187-8502, Japan; Tel: +81-423-41-2711; Fax: +81-423-16-1747; E-mail: araki@ncnp.go.jp


Abstract

The cerebral accumulation of β-amyloid protein (Aβ) is thought to play a key role in the molecular pathology of Alzheimer’s disease (AD). Recent evidence indicates that both β-secretase and γ-secretase, the membrane-associated proteases directly involved in the generation of Aβ from its precursor, amyloid precursor protein (APP), are localized to cholesterol-rich membrane microdomains termed lipid rafts. This underscores the significance of lipid rafts in the amyloidogenic processing of APP. In the present mini-review, I summarize recent research developments that shed light on the association of β-secretase and γ-secretase with lipid rafts, and discuss their implications for the pathology and therapeutics of AD.

Keywords: Alzheimer’s disease, amyloid precursor protein, β-amyloid, BACE1, cholesterol, lipid raft, γ-secretase.