Alpha-synuclein spreading in Parkinson’s disease

Ariadna Recasens, Benjamin Dehay
Front. Neuroanat.. 2014-12-18; 8:
DOI: 10.3389/fnana.2014.00159

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Recasens A(1), Dehay B(2).

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.

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.

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