Inflammatory Responses to Monomeric and Aggregated α-Synuclein in Peripheral Blood of Parkinson Disease Patients

• Main Authors: Federica Piancone, Marina Saresella, Francesca La Rosa, Ivana Marventano, Mario Meloni, Jorge Navarro, Mario Clerici
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-03-01
• Series: Frontiers in Neuroscience
• Subjects: Parkinson’s disease; α-synuclein; inflammation; inflammasome; cytokines
• Online Access: https://www.frontiersin.org/articles/10.3389/fnins.2021.639646/full

To investigate whether different forms of α-synuclein (α-syn) proteins can induce inflammation and activate the NLRP3 inflammasome, we stimulated with monomeric or aggregated α-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 1β (IL-18), and IL-1β], 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 α-syn does not stimulate the NLRP3 inflammasome and that PD does not associate with alterations of intestinal permeability. Interestingly, though, IL-1β and IL-6 production was increased, whereas that of IL-10 was reduced in α-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.