Immune system responses in Parkinson's disease: Early and dynamic

• Type of Material: Article
• Authors: Malu Tansey, Emory University; Marina Romero-Ramos, Aarhus University
• Language: English
• Date: 2019-02-01
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/ejn.14290
• Title of Journal or Parent Work: EUROPEAN JOURNAL OF NEUROSCIENCE
• Volume: 49
• Issue: 3
• Start Page: 364
• End Page: 383
• Grant/Funding Information: Funding support was provided from the Michael J. Fox Foundation (MGT and MR-R), the National Institutes of Health (1RF1AG057247 and 5RF1AG057247, and 3RF1AG051514–01S1 (MGT)), the Bjarne Saxhof Fund administered through the Danish Parkinson’s Foundation (MR-R) and the AUFF AU IDEAS center NEURODIN (MR-R).
• Keywords: monocytes; SUBSTANTIA-NIGRA; REGULATORY T-CELLS; alpha-synuclein; T-cells; CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; Life Sciences & Biomedicine; GUT MICROBIOTA; BLOOD MONONUCLEAR-CELLS; SYNUCLEIN ACTIVATES MICROGLIA; Neurosciences & Neurology; AGGREGATED ALPHA-SYNUCLEIN; TUMOR-NECROSIS-FACTOR; auto-antibodies; DOPAMINERGIC NEURODEGENERATION; Science & Technology; neuroinflammation; Neurosciences; microglia
• Research Categories: Psychology, Cognitive; Biology, Neuroscience

Abstract

The neuropathological hallmarks of Parkinson's disease (PD) are the degeneration and death of dopamine-producing neurons in the ventral midbrain, the widespread intraneuronal aggregation of alpha-synuclein (α) in Lewy bodies and neurites, neuroinflammation, and gliosis. Signs of microglia activation in the PD brain postmortem as well as during disease development revealed by neuroimaging, implicate immune responses in the pathophysiology of the disease. Intensive research during the last two decades has advanced our understanding of the role of these responses in the disease process, yet many questions remain unanswered. A transformative finding in the field has been the confirmation that in vivo microglia are able to respond directly to pathological a-syn aggregates but also to neuronal dysfunction due to intraneuronal a-syn toxicity well in advance of neuronal death. In addition, clinical research and disease models have revealed the involvement of both the innate and adaptive immune systems. Indeed, the data suggest that PD leads not only to a microglia response, but also to a cellular and humoral peripheral immune response. Together, these findings compel us to consider a more holistic view of the immunological processes associated with the disease. Central and peripheral immune responses aimed at maintaining neuronal health will ultimately have consequences on neuronal survival. We will review here the most significant findings that have contributed to the current understanding of the immune response in PD, which is proposed to occur early, involve peripheral and brain immune cells, evolve as neuronal dysfunction progresses, and is likely to influence disease progression.