Inflammatory Responses To Monomeric And Aggregated Alpha-Synuclein In Peripheral Blood Of Parkinson Disease Patients

To investigate whether different forms of alpha-synuclein (alpha-syn) proteins can induce inflammation and activate the NLRP3 inflammasome, we stimulated with monomeric or aggregated alpha-syn peripheral blood mononuclear cells of Parkinson disease (PD) patients and age- and sex-matched healthy controls (HC). ASC-speck formation, i.e., the intracellular generation of functionally active inflammasome complexes, as well as the production of inflammasome-related [caspase-1, interleukin 1 beta (IL-18), and IL-1 beta], and pro-IL-6, or anti-IL-10 inflammatory cytokines were evaluated. Gastrointestinal permeability, suggested to be altered in PD, was also investigated by measuring plasma concentration of lipopolysaccharide (LPS) and I-FABP (fatty acid-binding protein). ASC-speck expression, as well as IL-18 and caspase-1 production and LPS and I-FABP plasma concentration, was comparable in PD and HC, indicating that alpha-syn does not stimulate the NLRP3 inflammasome and that PD does not associate with alterations of intestinal permeability. Interestingly, though, IL-1 beta and IL-6 production was increased, whereas that of IL-10 was reduced in alpha-syn-stimulated cells of PD compared to HC, suggesting that PD-associated neuroinflammation is not the consequence of the activation of the NLRP3 inflammasome but rather of an imbalance between proinflammatory and anti-inflammatory cytokines.