Ross Christopher A, Poirier Michelle A
Division of Neurobiology, Department of Psychiatry at Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.
Nat Rev Mol Cell Biol. 2005 Nov;6(11):891-8. doi: 10.1038/nrm1742.
Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.
神经退行性疾病通常涉及包含异常聚集蛋白的包涵体沉积。因此，有人提出蛋白聚集具有致病性。然而，多条证据表明包涵体并非毒性的主要原因，而可能代表一种细胞保护反应。聚集是蛋白构象变化和积聚的复杂多步骤过程。该过程中的早期物种可能毒性最强，也许是通过暴露如主链NH和CO基团等埋藏部分，这些基团在与其他细胞蛋白的异常相互作用中可作为氢键供体或受体。该模型意味着多种神经退行性疾病的发病机制是由共同机制引起的，并且可能产生共同的治疗靶点。
