Department of Demyelinating disease and Aging, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan.
Front Biosci (Landmark Ed). 2015 Jan 1;20(2):314-24. doi: 10.2741/4311.
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.
脑内淀粉样β-蛋白（Aβ）的积累被认为在阿尔茨海默病（AD）的分子病理学中起关键作用。三种蛋白酶（β-、γ-和α-分泌酶）是控制淀粉样前体蛋白产生 Aβ的蛋白酶。越来越多的证据表明，富含胆固醇的膜微区称为“脂筏”，参与 Aβ的生物发生和积累以及 Aβ介导的神经毒性。γ-分泌酶富含脂筏，脂筏被认为是 Aβ产生的重要部位。此外，位于脂筏中的 Aβ降解肽酶，如 Neprilysin，似乎在 Aβ代谢中起作用。这篇综述主要关注脂筏在 Aβ生物发生和代谢中的作用，涵盖了最近关于脂筏与三种分泌酶或 Aβ降解肽酶之间关系的研究。此外，简要总结了脂筏在 Aβ聚集和神经毒性中的意义。
