Fibrillar α-synuclein induces neurotoxic astrocyte activation via RIP kinase signaling and NF-κB.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the death of midbrain dopamine neurons. The pathogenesis of PD is poorly understood, though misfolded and/or aggregated forms of the protein α-synuclein have been implicated in several neurodegenerative disease processes, including neuroinflammation and astrocyte activation. Astrocytes in the midbrain play complex roles during PD, initiating both harmful and protective processes that vary over the course of the disease. However, despite their significant regulatory roles during neurodegeneration, the cellular and molecular mechanisms that promote pathogenic astrocyte activity remain mysterious. Here, we show that α-synuclein preformed fibrils (PFFs) induce pathogenic activation of human midbrain astrocytes, marked by

SUBMITTER: Chou TW 

PROVIDER: S-EPMC8325686 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature