Author:

Abstract:

α-Synuclein aggregation is considered to play a central role in multiple neurodegenerative diseases, such as Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB), but the exact relationship between -SYN aggregation and pathogenesis remains unclear. Synucleinopathies are determined by the deposition of α-synuclein aggregates but segregate in distinct pathological phenotypes and diagnostic criteria. α-Synuclein is recently shown to aggregate into different polymorphs or ‘strains’ and has led to the hypothesis that strains might account for the disctinct clinico-pathological traits within synucleinopathies. Intracerebral and intravenous injection of distinct α-synuclein assemblies, with distinct conformational properties, resulted in specific neuropathological hallmarks via seeding and strain-specific effects. These distinctive neurotoxic and pathological prion-like effects of α-synuclein strains might provide a basis for the heterogeneity observed in synucleinopathies and open new therapeutic opportunities such as targeting the degradation of α-synuclein higher molecular weight species.