Department of Neurology and Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, 94158, USA.
Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Mol Neurodegener. 2019 May 16;14(1):19. doi: 10.1186/s13024-019-0318-4.
Many neurodegenerative disorders, including Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis, are well known to involve the accumulation of disease-specific proteins. Less well known are the accumulations of another set of proteins, neuronal intermediate filaments (NFs), which have been observed in these diseases for decades. NFs belong to the family of cytoskeletal intermediate filament proteins (IFs) that give cells their shape; they determine axonal caliber, which controls signal conduction; and they regulate the transport of synaptic vesicles and modulate synaptic plasticity by binding to neurotransmitter receptors. In the last two decades, a number of rare disorders caused by mutations in genes that encode NFs or regulate their metabolism have been discovered. These less prevalent disorders are providing novel insights into the role of NF aggregation in the more common neurological disorders.
许多神经退行性疾病，包括帕金森病、阿尔茨海默病和肌萎缩侧索硬化症，众所周知与特定疾病蛋白的积累有关。但不太为人所知的是另一组蛋白质，神经元中间丝（NFs）的积累，这些积累在这些疾病中已经观察了几十年。NFs 属于细胞骨架中间丝蛋白（IFs）家族，赋予细胞形状；它们决定轴突口径，控制信号传导；它们通过与神经递质受体结合来调节突触小泡的运输，并调节突触可塑性。在过去的二十年中，发现了许多由编码 NFs 或调节其代谢的基因突变引起的罕见疾病。这些不太常见的疾病为 NF 聚集在更常见的神经疾病中的作用提供了新的见解。
