Alpha-synuclein and the prion hypothesis in Parkinson's disease

Protein intracellular inclusions within the central nervous system are hallmarks of several progressive neurodegenerative disorders in man. The protein constituents of those deposits and the affected regions within the brain differ from one neurodegenerative disorder to another. Until recently, the vicious circle consisting of spread, seeded assembly and accumulation over time within the central nervous system of misfolded proteins aggregates was thought to be restricted to the prion protein PrP. Recent reports suggest that other protein aggregates spread and amplify within the central nervous system leading to distinct diseases. How alpha-synuclein protein assemblies traffic between cells, amplify by recruiting endogenous monomeric alpha-synuclein and cause distinct synucleinopathies is unclear. I review here the experimental evidence supporting the propagation of alpha-synuclein mega-dalton assemblies in a manner similar to prion protein aggregates. I also describe how alpha-synuclein aggregates. I also explain why the aggregation of alpha-synuclein may lead to distinct synucleinopathies. (C) 2018 Elsevier Masson SAS. All rights reserved.