[Frontiers in Bioscience, Landmark, 20, 314-324, January 1, 2015]

Amyloid Beta-protein and lipid rafts: focused on biogenesis and catabolism

Wataru Araki 1 , Akira Tamaoka 2

1Department of Demyelinating disease and Aging, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan, 2Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Aβ biogenesis and lipid rafts
    3.1. APP, Aβ and lipid rafts
    3.2. Relationship between lipid rafts and β-secretase
    3.3. Relationship between lipid rafts and α-secretase
    3.4. Relationship between lipid rafts and γ-secretase
4. Aβ catabolism and lipid rafts
5. Aβ aggregation, neurotoxicity and lipid rafts
6. Conclusions
7. Acknowledgments
8. References

1. ABSTRACT

Cerebral accumulation of amyloid β-protein (Aβ) is thought to play a key role in the molecular pathology of Alzheimer’s disease (AD). Three secretases (β-, γ-, and α-secretase) are proteases that control the production of Aβ from amyloid precursor protein. Increasing evidence suggests that cholesterol-rich membrane microdomains termed ‘lipid rafts’ are involved in the biogenesis and accumulation of Aβ as well as Aβ-mediated neurotoxicity. γ-Secretase is enriched in lipid rafts, which are considered an important site for Aβ generation. Additionally, Aβ-degrading peptidases located in lipid rafts, such as neprilysin, appear to play a role in Aβ catabolism. This mini-review focuses on the roles of lipid rafts in the biogenesis and catabolism of Aβ, covering recent research on the relationship between lipid rafts and the three secretases or Aβ-degrading peptidases. Furthermore, the significance of lipid rafts in Aβ aggregation and neurotoxicity is briefly summarized.

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Key Words: Alzheimer’s Disease, Amyloid β-Protein, ADAM10, BACE1, cholesterol, γ-Secretase, Lipid Rafts, Neprilysin, Review

Send correspondence to: Wataru Araki, Department of Demyelinating disease and Aging, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigahi, Kodaira, Tokyo 187-8502, Japan, Tel: 81-42-346-1717, Fax: 81-42-346-1747, E-mail: araki@ncnp.go.jp