Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity.
Int J Mol Sci
; 24(17)2023 Aug 25.
Article
en En
| MEDLINE
| ID: mdl-37686005
ABSTRACT
Alpha-synucleinopathies (α-synucleinopathies) such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are all characterized by aggregates of alpha-synuclein (α-syn), but display heterogeneous clinical and pathological phenotypes. The mechanism underlying this heterogeneity is thought to be due to diversity in the α-syn strains present across the diseases. α-syn obtained from the post-mortem brain of patients who lived with these conditions is heterogenous, and displays a different protease sensitivity, ultrastructure, cytotoxicity, and seeding potential. The primary aim of this review is to summarize previous studies investigating these concepts, which not only reflect the idea of different syn strains being present, but demonstrate that each property explains a small part of a much larger puzzle. Strains of α-syn appear at the center of the correlation between α-syn properties and the disease phenotype, likely influenced by external factors. There are considerable similarities in the properties of disease-specific α-syn strains, but MSA seems to consistently display more aggressive traits. Elucidating the molecular underpinnings of heterogeneity amongst α-synucleinopathies holds promise for future clinical translation, allowing for the development of personalized medicine approaches tackling the root cause of each α-synucleinopathy.
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Bases de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
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Atrofia de Múltiples Sistemas
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Demencia
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Sinucleinopatías
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido