alpha-synuclein has been researched along with aluminum-sulfate* in 1 studies
1 other study(ies) available for alpha-synuclein and aluminum-sulfate
Article | Year |
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Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein α-synuclein.
The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well. Topics: alpha-Synuclein; Alum Compounds; Caspase 1; Cell Line, Tumor; Cell Survival; Dipeptides; Gene Expression Regulation; Humans; Inflammasomes; Interleukin-1beta; Lewy Bodies; Lipopolysaccharides; Neurons; Nigericin; para-Aminobenzoates; Protein Aggregates; RNA, Small Interfering; Signal Transduction; Vitamin K 3 | 2016 |