Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 20, Issue -, Pages 314-324Publisher
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4311
Keywords
Alzheimer's Disease; Amyloid beta-Protein; ADAM10; BACE1; cholesterol; gamma-Secretase; Lipid Rafts; Neprilysin; Review
Categories
Funding
- Ministry of Health, Labor, and Welfare, Japan
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Grants-in-Aid for Scientific Research [25461300] Funding Source: KAKEN
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Cerebral accumulation of amyloid beta-protein (Ab) is thought to play a key role in the molecular pathology of Alzheimer's disease (AD). Three secretases (beta-, gamma-, and alpha-secretase) are proteases that control the production of A beta from amyloid precursor protein. Increasing evidence suggests that cholesterol-rich membrane microdomains termed 'lipid rafts' are involved in the biogenesis and accumulation of A beta as well as A beta-mediated neurotoxicity gamma-Secretase is enriched in lipid rafts, which are considered an important site for A beta generation. Additionally, A beta-degrading peptidases located in lipid rafts, such as neprilysin, appear to play a role in A beta catabolism. This mini-review focuses on the roles of lipid rafts in the biogenesis and catabolism of A beta, covering recent research on the relationship between lipid rafts and the three secretases or A beta-degrading peptidases. Furthermore, the significance of lipid rafts in A beta aggregation and neurotoxicity is briefly summarized.
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