Recasens Ariadna, Dehay Benjamin
Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute - Center for Networked Biomedical Research on Neurodegenerative Diseases Barcelona, Spain.
Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293 Bordeaux, France ; Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique, UMR 5293 Bordeaux, France.
Front Neuroanat. 2014 Dec 18;8:159. doi: 10.3389/fnana.2014.00159. eCollection 2014.
Formation and accumulation of misfolded protein aggregates are a central hallmark of several neurodegenerative diseases. In Parkinson's disease (PD), the aggregation-prone protein alpha-synuclein (α-syn) is the culprit. In the past few years, another piece of the puzzle has been added with data suggesting that α-syn may self-propagate, thereby contributing to the progression and extension of PD. Of particular importance, it was the seminal observation of Lewy bodies (LB), a histopathological signature of PD, in grafted fetal dopaminergic neurons in the striatum of PD patients. Consequently, these findings were a conceptual breakthrough, generating the "host to graft transmission" hypothesis, also called the "prion-like hypothesis." Several in vitro and in vivo studies suggest that α-syn can undergo a toxic templated conformational change, spread from cell to cell and from region to region, and initiate the formation of "LB-like aggregates," contributing to the PD pathogenesis. Here, we will review and discuss the current knowledge for such a putative mechanism on the prion-like nature of α-syn, and discuss about the proper use of the term prion-like.
错误折叠的蛋白质聚集体的形成和积累是几种神经退行性疾病的核心特征。在帕金森病（PD）中，易于聚集的蛋白质α-突触核蛋白（α-syn）是罪魁祸首。在过去几年中，又有新的数据为这一谜题增添了新内容，表明α-syn可能会自我传播，从而促进PD的进展和扩散。特别重要的是，在PD患者纹状体中移植的胎儿多巴胺能神经元中观察到路易小体（LB），这是PD的一种组织病理学特征。因此，这些发现是一个概念上的突破，产生了“宿主到移植物传播”假说，也称为“朊病毒样假说”。多项体外和体内研究表明，α-syn可发生有毒的模板化构象变化，在细胞间和区域间传播，并引发“LB样聚集体”的形成，从而导致PD的发病机制。在此，我们将回顾和讨论关于α-syn朊病毒样性质的这种假定机制的现有知识，并讨论“朊病毒样”一词的正确使用。
