Experimental Laboratory of Neurodegenerative Diseases, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City 14269, Mexico.
Facultad de Ciencias de la Salud, Autonomous University of Baja California (UABC), Valle de las Palmas, Mexicali 21100, Mexico.
Int J Mol Sci. 2022 Oct 11;23(20):12092. doi: 10.3390/ijms232012092.
The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each presenting different levels of toxicity. Aβ peptides can be internalized by particular receptors and trigger changes from Tau phosphorylation to alterations in cognitive function, through dysfunction of the cholinergic system. The goal of this review is to summarize the current knowledge on the role of lipids in Alzheimer's disease and their relationship with the basal cholinergic system, as well as potential disease-modifying therapies.
淀粉样 β (Aβ) 以神经突斑块 (NPs) 的形式存在的不溶性聚集物是定义阿尔茨海默病的主要特征之一。研究表明，这些肽在大脑中的积累对广泛的神经元丧失有重大贡献。此外，膜中胆固醇的含量和分布已被证明对 Aβ肽在质膜中的产生和随后的积累有重要影响，有助于功能障碍和神经元死亡。这些膜结合肽的单体形式经历了几种构象变化，从寡聚形式到β-折叠结构，每种形式都具有不同程度的毒性。Aβ肽可以被特定的受体内化，并通过胆碱能系统的功能障碍，引发从 Tau 磷酸化到认知功能改变的变化。本综述的目的是总结目前关于脂质在阿尔茨海默病中的作用及其与基底胆碱能系统的关系的知识，以及潜在的疾病修饰治疗方法。
