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

• Published in: Neurobiology of disease Vol. 109; no. Pt B; pp. 209 - 218
• Main Authors: Peng, Chao, Gathagan, Ronald J., Lee, Virginia M.-Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2018; Elsevier
• Subjects: alpha-Synuclein - chemistry; alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Animals; Dementia with Lewy body; Humans; Multiple system atrophy; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - therapy; Parkinson's disease; Protein aggregates; Protein Aggregation, Pathological - genetics; Protein Aggregation, Pathological - metabolism; Protein Aggregation, Pathological - therapy; Protein Conformation; α-Synuclein strains; α-Synucleinopathy; α-Synucleinopathy; Multiple system atrophy; Parkinson's disease; Dementia with Lewy body; α-Synuclein strains; Protein aggregates
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2017.07.018

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.