What’s to like about the prion-like hypothesis for the spreading of aggregated α-synuclein in Parkinson disease?

Abstract

α-Synuclein is a key protein in Parkinson disease. Not only is it the major protein component of Lewy bodies, but it is implicated in several cellular processes that are disrupted in Parkinson disease. Misfolded α-synuclein has also been shown to spread from cell-to-cell and, in a prion-like fashion, trigger aggregation of α-synuclein in the recipient cell. In this mini-review we explore the evidence that misfolded α-synuclein underlies the spread of pathology in Parkinson disease and discuss why it should be considered a prion-like protein.

Keywords: :

• Parkinson disease
• alpha-synuclein
• cell-to-cell transfer
• prion-like
• protein misfolding

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

Our work is supported by Michael J. Fox Foundation for Parkinson Research; Swedish Brain Foundation; Swedish Parkinson Foundation; Swedish Research Council, including the Linnaeus grant Bagadilico; European Research Area Network of European Funding for Neuroscience Research Program MIPROTRAN; Human Frontier Science Program; Swedish Brain Power; and a European Research Council Advanced Award. All authors are active in the Strong Research Environment Multipark (multidisciplinary research in Parkinson disease at Lund University).