肌萎缩侧索硬化
SOD1
运动神经元
发病机制
生物
包涵体
神经科学
蛋白质折叠
神经退行性变
细胞生物学
脊髓
遗传学
医学
病理
疾病
免疫学
基因
大肠杆菌
作者
Prajwal Ciryam,Isabella A. Lambert-Smith,Daniel Bean,Rosie Freer,Fernando Maureira Cid,Gian Gaetano Tartaglia,Darren N. Saunders,Mark R. Wilson,Stephen G. Oliver,Richard I. Morimoto,Christopher M. Dobson,Michele Vendruscolo,Giorgio Favrin,Justin J. Yerbury
标识
DOI:10.1073/pnas.1613854114
摘要
Significance Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with wide clinical variability and a complex pathogenesis. One of the hallmarks of ALS is the presence of diverse inclusions formed by apparently disparate misfolded proteins, which are unrelated in sequence, structure, function, and localization. Many of these proteins, in addition, are not the usual interaction partners of the primary inclusion-forming ALS-related proteins (SOD1, TDP-43, and FUS). Here, we show that a common feature of these coaggregating proteins is their metastability to aggregation in spinal motor neurons. These results suggest that as protein homeostasis becomes progressively impaired in ALS, supersaturated proteins in an ALS-specific group fail to be maintained in their soluble states, leading to their presence in ALS-associated inclusions.
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