Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Nat Med. 2014 Feb;20(2):130-8. doi: 10.1038/nm.3457.
A common feature of many neurodegenerative diseases is the deposition of β-sheet-rich amyloid aggregates formed by proteins specific to these diseases. These protein aggregates are thought to cause neuronal dysfunction, directly or indirectly. Recent studies have strongly implicated cell-to-cell transmission of misfolded proteins as a common mechanism for the onset and progression of various neurodegenerative disorders. Emerging evidence also suggests the presence of conformationally diverse 'strains' of each type of disease protein, which may be another shared feature of amyloid aggregates, accounting for the tremendous heterogeneity within each type of neurodegenerative disease. Although there are many more questions to be answered, these studies have opened up new avenues for therapeutic interventions in neurodegenerative disorders.
许多神经退行性疾病的一个共同特征是由这些疾病特有的蛋白质组成的富含β-折叠的淀粉样聚集物的沉积。这些蛋白质聚集物被认为直接或间接地导致神经元功能障碍。最近的研究强烈表明，错误折叠蛋白的细胞间传递是各种神经退行性疾病发病和进展的共同机制。新出现的证据还表明，每种疾病蛋白都存在构象多样的“菌株”，这可能是淀粉样聚集物的另一个共同特征，这解释了每种神经退行性疾病中存在的巨大异质性。尽管还有许多问题需要回答，但这些研究为神经退行性疾病的治疗干预开辟了新的途径。
