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Piancone F, Saresella M, La Rosa F, et al. Inflammatory Responses to Monomeric and Aggregated α-Synuclein in Peripheral Blood of Parkinson Disease Patients. Front Neurosci. 2021;15:639646doi: 10.3389/fnins.2021.639646.
Piancone, F., Saresella, M., La Rosa, F., Marventano, I., Meloni, M., Navarro, J., & Clerici, M. (2021). Inflammatory Responses to Monomeric and Aggregated α-Synuclein in Peripheral Blood of Parkinson Disease Patients. Frontiers in neuroscience, 15639646. https://doi.org/10.3389/fnins.2021.639646
Piancone, Federica, et al. "Inflammatory Responses to Monomeric and Aggregated α-Synuclein in Peripheral Blood of Parkinson Disease Patients." Frontiers in neuroscience vol. 15 (2021): 639646. doi: https://doi.org/10.3389/fnins.2021.639646
Piancone F, Saresella M, La Rosa F, Marventano I, Meloni M, Navarro J, Clerici M. Inflammatory Responses to Monomeric and Aggregated α-Synuclein in Peripheral Blood of Parkinson Disease Patients. Front Neurosci. 2021 Mar 25;15:639646. doi: 10.3389/fnins.2021.639646. eCollection 2021. PMID: 33867921; PMCID: PMC8044810.
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Front Neurosci. 2021 Mar 25;15:639646. doi: 10.3389/fnins.2021.639646. eCollection 2021.

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

Frontiers in neuroscience

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

Affiliations

  1. Laboratory of Molecular Medicine and Biotechnology, IRCCS Fondazione don C Gnocchi, Milan, Italy.
  2. Department of Neurology, IRCCS Fondazione don C Gnocchi, Milan, Italy.
  3. Department of Physiopathology and Transplants, University of Milano, Milan, Italy.

PMID: 33867921 PMCID: PMC8044810 DOI: 10.3389/fnins.2021.639646

Abstract

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.

Copyright © 2021 Piancone, Saresella, La Rosa, Marventano, Meloni, Navarro and Clerici.

Keywords: Parkinson’s disease; cytokines; inflammasome; inflammation; α-synuclein

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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