Internalized α-synuclein fibrils become truncated and resist degradation in neurons while glial cells rapidly degrade α-synuclein fibrils.

ABSTRACT: Parkinson's disease (PD) and other α-synucleinopathies are characterized by the intracellular aggregates of α-synuclein (αS) believed to spread via the cell-to-cell transmission. To understand the contributions of various brain cells to the spreading of αS pathology, we examined the metabolism of αS aggregates in neuronal and glial cells. In neurons, while the full-length αS rapidly disappeared following αS PFF uptake, truncated αS accumulated with a half-life of days rather than hours. Epitope mapping and fractionation studies indicate that αS fibrils internalized by neurons was truncated at the C-terminal region and remained insoluble. In contrast, microglia and astrocytes rapidly metabolized αS fibrils as the half-lives of αS fibrils in these glial cells were <6 hours. Differential upta

SUBMITTER: Karim MR 

PROVIDER: S-EPMC11185753 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature