Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies.

ABSTRACT: In Lewy body diseases-including Parkinson's disease, without or with dementia, dementia with Lewy bodies, and Alzheimer's disease with Lewy body co-pathology ¹ -α-synuclein (α-Syn) aggregates in neurons as Lewy bodies and Lewy neurites ² . By contrast, in multiple system atrophy α-Syn accumulates mainly in oligodendrocytes as glial cytoplasmic inclusions (GCIs) ³ . Here we report that pathological α-Syn in GCIs and Lewy bodies (GCI-α-Syn and LB-α-Syn, respectively) is conformationally and biologically distinct. GCI-α-Syn forms structures that are more compact and it is about 1,000-fold more potent than LB-α-Syn in seeding α-Syn aggregation, consistent with the highly aggressive nature of multiple system atrophy. GCI-α-Syn and LB-α-Syn show no cell-type pref

SUBMITTER: Peng C 

PROVIDER: S-EPMC5970994 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature