Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-2676, USA.
Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-2676, USA.
Trends Mol Med. 2020 Oct;26(10):936-952. doi: 10.1016/j.molmed.2020.03.012. Epub 2020 May 1.
The stereotypical spread of pathological protein inclusions and clinicopathological heterogeneity are well described in neurodegenerative diseases. Accumulating evidence suggests that the former can be attributed to consecutive cell-to-cell transmission of pathological proteins between anatomically connected brain regions, while the latter has been hypothesized to result from the spread of conformationally distinct pathological protein aggregates, or strains. These emerging concepts have dramatically changed our understanding of neurodegenerative diseases. In this review, we first summarize the background and recent findings underpinning these concepts with a focus on two major pathological proteins: tau and α-synuclein. We then discuss their clinical implications for tauopathies and synucleinopathies and propose a working hypothesis for future research.
在神经退行性疾病中，病理性蛋白包涵体的典型扩散和临床病理异质性得到了很好的描述。越来越多的证据表明，前者可以归因于病理蛋白在解剖上连接的脑区之间的连续细胞间传递，而后者则假设是由构象不同的病理性蛋白聚集物或株的扩散引起的。这些新出现的概念极大地改变了我们对神经退行性疾病的理解。在这篇综述中，我们首先总结了支持这些概念的背景和最新发现，重点介绍了两种主要的病理蛋白：tau 和 α-突触核蛋白。然后，我们讨论了它们对 tau 病和突触核蛋白病的临床意义，并为未来的研究提出了一个工作假设。
