Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA; The Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA.
Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA; The Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, USA.
Neuron. 2021 Jan 20;109(2):205-221. doi: 10.1016/j.neuron.2020.10.008. Epub 2020 Nov 10.
Apolipoprotein E (ApoE) is of great interest due to its role as a cholesterol/lipid transporter in the central nervous system (CNS) and as the most influential genetic risk factor for Alzheimer disease (AD). Work over the last four decades has given us important insights into the structure of ApoE and how this might impact the neuropathology and pathogenesis of AD. In this review, we highlight the history and progress in the structural and molecular understanding of ApoE and discuss how these studies on ApoE have illuminated the physiology of ApoE, receptor binding, and interaction with amyloid-β (Aβ). We also identify future areas of study needed to advance our understanding of how ApoE influences neurodegeneration.
载脂蛋白 E(ApoE)作为中枢神经系统(CNS)中的胆固醇/脂质转运蛋白,以及阿尔茨海默病(AD)最具影响力的遗传风险因素,备受关注。过去四十年的研究使我们对 ApoE 的结构有了重要的了解,并且深入探讨了这将如何影响 AD 的神经病理学和发病机制。在本综述中,我们重点介绍了 ApoE 的结构和分子理解方面的历史和进展,并讨论了这些关于 ApoE 的研究如何阐明了 ApoE 的生理学、受体结合以及与淀粉样蛋白-β(Aβ)的相互作用。我们还确定了未来需要研究的领域,以增进我们对 ApoE 如何影响神经退行性变的理解。