Alpha-Synuclein Aggregates Activate the Nlrp3 Inflammasome Following Vesicle Rupture
Year: 2013
Type: dissertation
Abstract: Parkinson's disease (PD) and related synucleinopathies are progressive neurodegenerative disorders that feature the accumulation of intracellular inclusions known as Lewy bodies (LBs) in the brain. The presynaptic protein α-synuclein is the primary constituent of LBs and has been documented to play a major role in the pathogenesis of synucleinopathies. Recently, aggregated α-synuclein has been implicated in prompting microglia-mediated inflammation, a process associated with the progression of neuronal death in neurodegenerative disorders. Although the mechanisms surrounding the induction of neuroinflammation are not well understood, the recently discovered inflammasome-forming NLR proteins have emerged as regulators of inflammation. In this study, we sought to understand the involvement of the inflammasome in response to aggregated α-synuclein in microglia-like cells. We report that aggregated α-synuclein induces vesicle rupture in THP-1 cells that is sensed as a `danger signal' resulting in the assembly of the NLRP3 inflammasome, activation of caspase-1, and the release of proinflammatory cytokines.
Author: Rudy Orlando Cedillos
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W213463352