期刊
CURRENT OPINION IN NEUROLOGY
卷 29, 期 4, 页码 459-466出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WCO.0000000000000349
关键词
alpha-synuclein; Lewy body; Parkinson's disease; prion-like
资金
- Van Andel Institute
- Renovo
- Teva/Lundbeck
- National Institutes of Health [R01NS071035, R01NS060729, 1R01NS094460-01, R01NS070577, R21NS093993-01]
Purpose of review We describe evidence supporting the hypothesis that alpha-synuclein has a prion-like role in Parkinson's disease and related alpha-synucleinopathies, and discuss how this novel thinking impacts the development of diagnostics and disease-modifying therapies. Recent findings Observations that immature dopamine neurons grafted to Parkinson's disease patients can develop Lewy bodies triggered a surge of interest in the putative prion-like properties of alpha-synuclein. We recount results from experiments which confirm that misfolded alpha-synuclein can exhibit disease-propagating properties, and describe how they relate to the spreading of alpha-synuclein aggregates in alpha-synucleinopathies. We share insights into the underlying molecular mechanisms and their relevance to novel therapeutic targets. Finally, we discuss what the initial triggers of alpha-synuclein misfolding might be, where in the body the misfolding events might take place, and how this can instruct development of novel diagnostic tools. We speculate that differences in anatomical trigger sites and variability in alpha-synuclein fibril structure can contribute to clinical differences between alpha-synucleinopathies. Summary The realization that alpha-synuclein pathology can propagate between brain regions in neurodegenerative diseases has deepened and expanded our understanding of potential pathogenic processes which can lead to the development of novel diagnostic tools as well as the identification of new therapeutic targets.
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