Department of Biochemistry, SBBS, Queen Mary, University of London, UK.
Angew Chem Int Ed Engl. 2023 Jun 19;62(25):e202215785. doi: 10.1002/anie.202215785. Epub 2023 Mar 30.
The accumulation of the amyloid-β peptides (Aβ) is central to the development of Alzheimer's disease. The mechanism by which Aβ triggers a cascade of events that leads to dementia is a topic of intense investigation. Aβ self-associates into a series of complex assemblies with different structural and biophysical properties. It is the interaction of these oligomeric, protofibril and fibrillar assemblies with lipid membranes, or with membrane receptors, that results in membrane permeability and loss of cellular homeostasis, a key event in Alzheimer's disease pathology. Aβ can have an array of impacts on lipid membranes, reports have included: a carpeting effect; a detergent effect; and Aβ ion-channel pore formation. Recent advances imaging these interactions are providing a clearer picture of Aβ induced membrane disruption. Understanding the relationship between different Aβ structures and membrane permeability will inform therapeutics targeting Aβ cytotoxicity.
淀粉样蛋白-β（Aβ）的积累是阿尔茨海默病发展的核心。Aβ引发导致痴呆的级联事件的机制是一个研究热点。Aβ 自身缔合形成一系列具有不同结构和生物物理特性的复杂组装体。正是这些寡聚体、原纤维和纤维组装体与脂膜或膜受体的相互作用导致了膜通透性和细胞内稳态的丧失，这是阿尔茨海默病病理的关键事件。有报道称，Aβ 对脂膜有多种影响，包括：地毯效应；去污剂效应；以及 Aβ 离子通道孔形成。最近在成像这些相互作用方面的进展提供了更清晰的 Aβ 诱导的膜破坏图像。了解不同 Aβ 结构与膜通透性之间的关系，将为针对 Aβ 细胞毒性的治疗提供信息。
