title: Alpha-synuclein spreading in Parkinson's disease.
abstract: 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.
authors.affiliation: Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute - Center for Networked Biomedical Research on Neurodegenerative Diseases Barcelona, Spain.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Recasens
authors.affiliation: 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.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dehay
keywords: Parkinson disease; aggregation; neurodegenerative diseases; spreading; α-synuclein