Inflammation in Parkinson's disease: Mechanisms and therapeutic implications

Parkinson's disease (PD) is a common neurodegenerative disorder primarily characterized by the death of dopaminergic neurons that project from the substantia nigra pars compacta. Although the molecular bases for PD development are still little defined, extensive evidence from human samples and animal models support the involvement of inflammation in onset or progression. However, the exact trigger for this response remains unclear. Here, we provide a systematic review of the cellular mediators, i.e., microglia, astroglia and endothelial cells. We also discuss the genetic and transcriptional control of inflammation in PD and the immunomodulatory role of dopamine and reactive oxygen species. Finally, we summarize the preclinical and clinical approaches targeting neuroinflammation in PD.This work was supported by PID2019-110061RB-I00 and SAF2017-82436R of the Spanish Ministry of Economy and Competiveness; P-024-FTPGB 2018 from the Spanish “Tatiana de Guzman el Bueno Foundation” and by the P_37_732/2016 grant (REDBRAIN) financed by the European Regional Development Fund, Competitiveness Operational Program 2014–2020. Comunidad Autónoma de Madrid (grants B2017/BMD-3827, S2017-BMD-3686). MP is recipient of a contract Juan de la Cierva (MICINN)