From inflammasome to Parkinson's disease: Does the NLRP3 inflammasome facilitate exosome secretion and exosomal alpha-synuclein transmission in Parkinson's disease?

From inflammasome to Parkinson's disease: Does the NLRP3 inflammasome facilitate exosome secretion and exosomal alpha-synuclein transmission in Parkinson's disease? Exp Neurol. 2020 Nov 05;:113525 Authors: Si XL, Fang YJ, Li LF, Gu LY, Yin XZ, Jun-Tian, Yan YP, Pu JL, Zhang BR Abstract A pivotal neuropathological manifestation of synucleinopathies, like Parkinson's disease (PD), is the aggregation of α-synuclein. In a recent cell-to-cell transmission model of α-synuclein, α-synuclein propagation was demonstrated to resemble that of prion proteins in the central nervous system. Furthermore, exosomes, as biomolecule carriers, have been shown to transmit α-synuclein from neuron to neuron. However, the mechanisms underlying exosomal α-synuclein transmission have not been well understood. The NLR family pyrin domain containing 3 protein (NLRP3) inflammasome activation in microglia, and the subsequent release of proinflammatory cytokines, are two crucial pathological events involved in neuroinflammation and PD progression. Research has revealed that the NLRP3 inflammasome may facilitate the secretion of extracellular vesicles, as well as exosomal transmission of proteins like aggregated α-synuclein. However, only a few reports have evaluated these pathogenic mechanisms. Herein we evaluate for the first time the current evidence for the involvement of the NLRP3 inflammasome in microvesicle generation by microglial cells, and the vario...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research