Estes Raja Elizabeth, Lin Bernice, Khera Arnav, Davis Marie Ynez
VA Puget Sound Health Care System, Seattle, WA, United States.
Division of Biological Sciences, University of Montana, Missoula, MT, United States.
Front Mol Neurosci. 2021 Dec 20;14:788695. doi: 10.3389/fnmol.2021.788695. eCollection 2021.
Many neurodegenerative diseases are characterized by abnormal protein aggregates, including the two most common neurodegenerative diseases Alzheimer's disease (AD) and Parkinson's disease (PD). In the global search to prevent and treat diseases, most research has been focused on the early stages of the diseases, including how these pathogenic protein aggregates are initially formed. We argue, however, that an equally important aspect of disease etiology is the characteristic of protein aggregates throughout the nervous system, a key process in disease progression. Growing evidence suggests that both alterations in lipid metabolism and dysregulation of extracellular vesicles (EVs) accelerate the spread of protein aggregation and progression of neurodegeneration, both in neurons and potentially in surrounding glia. We will review how these two pathways are intertwined and accelerate the progression of AD and PD. Understanding how lipid metabolism, EV biogenesis, and EV uptake regulate the spread of pathogenic protein aggregation could reveal novel therapeutic targets to slow or halt neurodegenerative disease progression.
许多神经退行性疾病的特征是异常蛋白质聚集体，包括两种最常见的神经退行性疾病——阿尔茨海默病（AD）和帕金森病（PD）。在全球范围内预防和治疗疾病的探索中，大多数研究都集中在疾病的早期阶段，包括这些致病性蛋白质聚集体最初是如何形成的。然而，我们认为，疾病病因学的一个同样重要的方面是整个神经系统中蛋白质聚集体的特征，这是疾病进展中的一个关键过程。越来越多的证据表明，脂质代谢改变和细胞外囊泡（EV）失调都会加速蛋白质聚集的传播以及神经退行性变在神经元和潜在的周围神经胶质细胞中的进展。我们将综述这两条途径是如何相互交织并加速AD和PD进展的。了解脂质代谢、EV生物发生和EV摄取如何调节致病性蛋白质聚集的传播，可能会揭示出减缓或阻止神经退行性疾病进展的新治疗靶点。
