The Open Biology Journal

2010, 3 : 16-20
Published online 2010 March 19. DOI: 10.2174/18741967010030100016
Publisher ID: TOBIOJ-3-16

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.

* 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.