Soluble endogenous oligomeric ?-synuclein species in neurodegenerative diseases: Expression, spreading, and cross-talk.

ABSTRACT: There is growing recognition in the field of neurodegenerative diseases that mixed proteinopathies are occurring at greater frequency than originally thought. This is particularly true for three amyloid proteins defining most of these neurological disorders, amyloid-beta (A?), tau, and alpha-synuclein (?Syn). The co-existence and often co-localization of aggregated forms of these proteins has led to the emergence of concepts positing molecular interactions and cross-seeding between A?, tau, and ?Syn aggregates. Amongst this trio, ?Syn has received particular attention in this context during recent years due to its ability to modulate A? and tau aggregation in vivo, to interact at a molecular level with A? and tau in vivo and to cross-seed tau in mice. Here we provide a comprehensive, critical, and accessible review about the expression, role and nature of endogenous soluble ?Syn oligomers because of recent developments in the understanding of ?Syn multimerization, misfolding, aggregation, cross-talk, spreading and cross-seeding in neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, Alzheimer's disease, and Huntington's disease. We will also discuss our current understanding about the relative toxicity of endogenous ?Syn oligomers in vivo and in vitro, and introduce potential opportunities to counter their deleterious effects.

SUBMITTER: Kayed R 

PROVIDER: S-EPMC7458533 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature