Skin-derived α-synuclein strains from PD, DLB, and MSA induce distinct intracellular pathology and neurodegeneration.

ABSTRACT: α-Synuclein (αSyn) aggregates ("strains") can be detected by seed amplification assays such as real-time quaking-induced conversion from the skin of patients with synucleinopathies including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, whether skin-derived αSyn strains induce disease-specific pathology in a biological system is unknown. We have identified a human glioblastoma cell line U251 that readily forms intracellular αSyn inclusions upon seeding by exogenous αSyn seeds. These intracellular αSyn inclusions are detergent-insoluble and colocalize with phosphorylated-αSyn at serine 129 (p-αSyn), the pathological hallmark of synucleinopathies. We have engineered a Förster resonance energy transfer-based αSyn biosensor in U251 cells

SUBMITTER: Raina A 

PROVIDER: S-EPMC12805178 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature