AUTHOR=Piancone Federica , Saresella Marina , La Rosa Francesca , Marventano Ivana , Meloni Mario , Navarro Jorge , Clerici Mario 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 15 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.639646

DOI=10.3389/fnins.2021.639646

ISSN=1662-453X

ABSTRACT=To investigate whether different forms of α-syn proteins can induce inflammation and activate the NLRP3 inflammasome, we stimulated with monomeric or aggregated α-syn LPS-primed peripheral blood mononuclear cells (PBMC) of 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, 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 LPS and I-FABP.
ASC-speck expression as well as IL-18 and Caspase-1 production and LPS and I-FABP plasma concentration were comparable in PD and HC, indicating that α-syn does not stimulate the NLRP3 inflammasome activity 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 pro- and anti-inflammatory cytokines.