Institut François-Jacob, MIRCen, CEA, laboratory of Neurodegenerative Diseases, CNRS, 18, route du Panorama, 92265 Fontenay-aux-Roses cedex, France.
Rev Neurol (Paris). 2018 Nov;174(9):644-652. doi: 10.1016/j.neurol.2018.08.002. Epub 2018 Sep 7.
Protein intracellular inclusions within the central nervous system are hallmarks of several progressive neurodegenerative disorders in man. The protein constituents of those deposits and the affected regions within the brain differ from one neurodegenerative disorder to another. Until recently, the vicious circle consisting of spread, seeded assembly and accumulation over time within the central nervous system of misfolded proteins aggregates was thought to be restricted to the prion protein PrP. Recent reports suggest that other protein aggregates spread and amplify within the central nervous system leading to distinct diseases. How alpha-synuclein protein assemblies traffic between cells, amplify by recruiting endogenous monomeric alpha-synuclein and cause distinct synucleinopathies is unclear. I review here the experimental evidence supporting the propagation of alpha-synuclein mega-dalton assemblies in a manner similar to prion protein aggregates. I also describe how alpha-synuclein aggregates. I also explain why the aggregation of alpha-synuclein may lead to distinct synucleinopathies.
中枢神经系统内的蛋白质细胞内包涵体是人类几种进行性神经退行性疾病的标志。这些沉积物的蛋白质成分和大脑内受影响的区域因神经退行性疾病的不同而不同。直到最近，人们还认为由错误折叠的蛋白质聚集体在中枢神经系统内的传播、种子组装和随时间积累所构成的恶性循环仅限于朊病毒蛋白 PrP。最近的报告表明，其他蛋白质聚集体在中枢神经系统内传播和放大，导致不同的疾病。α-突触核蛋白组装体如何在细胞间运输，通过招募内源性单体α-突触核蛋白进行扩增，并导致不同的突触核蛋白病尚不清楚。我在这里回顾了支持α-突触核蛋白 mega-道尔顿组装体以类似于朊病毒蛋白聚集体的方式传播的实验证据。我还描述了α-突触核蛋白聚集体的形成方式。我还解释了为什么α-突触核蛋白的聚集可能导致不同的突触核蛋白病。
