Distinct α-Synuclein strains and implications for heterogeneity among α-Synucleinopathies

• Main Authors: Chao Peng, Ronald J. Gathagan, Virginia M.-Y. Lee
• Format: Article
• Language: English
• Published: Elsevier 2018-01-01
• Series: Neurobiology of Disease
• Subjects: α-Synuclein strains; Protein aggregates; α-Synucleinopathy; Multiple system atrophy; Parkinson's disease; Dementia with Lewy body
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996117301705

The deposition of misfolded β-sheet enriched amyloid protein is a shared feature of many neurodegenerative diseases. Recent studies demonstrated the existence of conformationally diverse strains as a common property for multiple amyloidogenic proteins including α-Synuclein (α-Syn). α-Syn is misfolded and aggregated in a group of neurodegenerative diseases collectively known as α-Synucleinopathies, which include Parkinson's disease (PD), dementia with Lewy body, multiple system atrophy and also a subset of Alzheimer's disease patients with concomitant PD-like Lewy bodies and neurites. While sharing the same pathological protein, different α-Synucleinopathies demonstrate distinct clinical and pathological phenotypes, which could result from the existence of diverse pathological α-Syn strains in patients. In this review, we summarized the characteristics of different α-Synucleinopathies and α-Syn strains generated with recombinant α-Syn monomers. We also make predictions of α-Syn strains that could potentially exist in patients based on the knowledge from other amyloid proteins and the clinical and pathological features of different α-Synucleinopathies.