Inflammation and immune dysfunction in Parkinson disease

• Type of Material: Article
• Authors: MariadeLourdes Tansey, Emory University; Rebecca L Wallings, University of Florida; Madelyn Houser, Emory University; Mary K Herrick, University of Florida; Cody E Keating, University of Florida; Valerie Joers, University of Florida
• Language: English
• Date: 2022-03-04
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © Springer Nature Limited 2022
• Final Published Version (URL): http://dx.doi.org/10.1038/s41577-022-00684-6
• Title of Journal or Parent Work: NATURE REVIEWS IMMUNOLOGY
• Grant/Funding Information: The authors’ research is supported by grants from the US National Institutes of Health (NS092122, AG051514, AG057247 to M.G.T.), the Michael J. Fox Foundation for Parkinson’s Research (16778.01, 18212, 18319, 18891 to M.G.T., V.J. and R.L.W.) and the Parkinson Foundation (PF-RCE-1945 to M.G.T.). The authors regret that several important studies could only be cited indirectly through comprehensive reviews, owing to space and reference number limitations.
• Keywords: SYNUCLEIN GENE DUPLICATION; Life Sciences & Biomedicine; MOUSE MODEL; REPEAT KINASE LRRK2; IFN-GAMMA; GENOME-WIDE ASSOCIATION; DOPAMINERGIC-NEURONS; NECROSIS-FACTOR-ALPHA; Science & Technology; CEREBROSPINAL-FLUID; Immunology; INTERFERON-GAMMA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS
• Research Categories: Health Sciences, Nursing; Biology, Neuroscience

Abstract

Parkinson disease (PD) is a progressive neurodegenerative disease that affects peripheral organs as well as the central nervous system and involves a fundamental role of neuroinflammation in its pathophysiology. Neurohistological and neuroimaging studies support the presence of ongoing and end-stage neuroinflammatory processes in PD. Moreover, numerous studies of peripheral blood and cerebrospinal fluid from patients with PD suggest alterations in markers of inflammation and immune cell populations that could initiate or exacerbate neuroinflammation and perpetuate the neurodegenerative process. A number of disease genes and risk factors have been identified as modulators of immune function in PD and evidence is mounting for a role of viral or bacterial exposure, pesticides and alterations in gut microbiota in disease pathogenesis. This has led to the hypothesis that complex gene-by-environment interactions combine with an ageing immune system to create the ‘perfect storm’ that enables the development and progression of PD. We discuss the evidence for this hypothesis and opportunities to harness the emerging immunological knowledge from patients with PD to create better preclinical models with the long-term goal of enabling earlier identification of at-risk individuals to prevent, delay and more effectively treat the disease.