Are synucleinopathies prion-like disorders?

作者：Angot Elodie; Steiner Jennifer A; Hansen Christian; Li Jia Yi; Brundin Patrik^*

来源：Lancet Neurology, 2010, 9(11): 1128-1138.

DOI：10.1016/S1474-4422(10)70213-1

A shared neuropathological feature of idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy is the development of intracellular aggregates of alpha-synuclein that gradually engage increasing parts of the nervous system. The pathogenetic mechanisms underlying these neurodegenerative disorders, however, are unknown. Several studies have highlighted similarities between classic prion diseases and these neurological proteinopathies. Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that alpha-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons. These results and others have led to the hypothesis that a prion-like mechanism might underlie progression of synucleinopathy within the nervous system. We review experimental findings showing that misfolded alpha-synuclein can transfer between cells and, once transferred into a new cell, can act as a seed that recruits endogenous alpha-synuclein, leading to formation of larger aggregates. This model suggests that strategies aimed at prevention of cell-to-cell transfer of alpha-synuclein could retard progression of symptoms in Parkinson's disease and other synucleinopathies.

• 出版日期2010-11