Gene Dysfunction Mediates Immune Response to Dopaminergic Degeneration in Parkinson's Disease

Many publications reported that genetic dysfunction mediates abnormal immune responses in the brain, which is important for the development of neurodegenerative diseases, especially for Parkinson's disease (PD). This immune disorder results in subsequent inflammatory reaction, which stimulates microglia or other immune cells to secrete cytokines and chemokines and disturbs the proportion of peripheral blood lymphocyte subsets contributing to dopaminergic (DA) neuron apoptosis. Furthermore, the abnormal immune related signal pathways caused by genetic variants promote chronic inflammation destroying the blood-brain barrier, which allows infiltration of different molecules and blood cells into the central nervous system (CNS) exerting toxicity on DA neurons. As a result, the inflammatory reaction in the CNS accelerates the progression of Parkinson's disease and promotes α-synuclein aggregation and diffusion among DA neurons in the procession of Parkinson's disease. Thus, for disease evaluation, the genetic mediated abnormal immune response in PD may be assessed based on the multiple immune molecules and inflammatory factors, as well as the ratio of lymphocyte subsets from PD patient's peripheral blood as potential biomarkers.