Pathological α-synuclein exacerbates the progression of Parkinson's disease through microglial activation

Parkinson's disease (PD) is characterized by alpha-synuclein accumulation, dopaminergic neuron loss and inflammation. alpha-Synuclein can be secreted by neurons and activate microglia to different degrees. Excessive microglial activation can increase the production of tumor necrosis factor alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), interleukin-6 (IL-6), interferon-gamma (INF-gamma), inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS) and nitric oxide (NO), and can also enhance microglial phagocytosis and migration as well as lymphocyte infiltration. Pathological alpha-synuclein and microglial activation can potentiate each other, leading to the loss of dopaminergic neurons and accelerated PD degeneration. This review will mainly describe the profiles of alpha-synuclein-activated microglia, with particular emphasis on the signaling cascades involved in this process. (C) 2016 Elsevier Ireland Ltd. All rights reserved.