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Front Neuroanat. 2014 Dec 18;8:159. doi: 10.3389/fnana.2014.00159. eCollection 2014.

Alpha-synuclein spreading in Parkinson's disease.

Author information

1
Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute - Center for Networked Biomedical Research on Neurodegenerative Diseases Barcelona, Spain.
2
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.

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.

KEYWORDS:

Parkinson disease; aggregation; neurodegenerative diseases; spreading; α-synuclein

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