NEUROINFLAMMATION AND IMMUNE DYSFUNCTION IN THE PATHOGENESIS OF PARKINSON’S DISEASE

Abstract

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder, characterized by dopaminergic neuronal loss, aggregation of alpha-synuclein and severe motor impairments. This review summarizes current data on the key role of neuroinflammation and immune dysfunction in neurodegeneration and disease development. We examine clinical and experimental evidence for microglia activation, participation of Toll-like receptors in this process, a wide range of chemokines and pro- and anti-inflammatory cytokines in the course of the disease. Emphasis is also made on the impact of the innate and adaptive immune responses in the mechanisms of systemic inflammation both in the brain and in the periphery. The involvement of brain-infiltrating immune cells and their subpopulations in the process of neuroinflammation and neurodegeneration, changes in the composition and phenotype of peripheral immune cells and their functional characteristics are discussed. Analysis of immune cell subsets and their ratios reveals subtle PD-specific changes in cellular populations that can be used as reliable biomarkers for diagnosis, prognosis of the disease course, and development of new approaches for anti-inflammatory and targeted therapies in PD.