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

• Published in: Toxicology letters Vol. 265; pp. 30 - 37
• Main Authors: Zhang, Qiu-Shuang, Heng, Yang, Yuan, Yu-He, Chen, Nai-Hong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 04.01.2017
• Subjects: alpha-Synuclein - metabolism; Disease Progression; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Humans; Inflammation; Microglia; Microglia - immunology; Microglia - metabolism; Neuroimmunomodulation - immunology; Oxidative Stress - immunology; Parkinson Disease - immunology; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson’s disease; Phagocytosis - immunology; Signal Transduction - immunology; α-synuclein; SH-SY5Y; JNK; AP-1; CD11b; INF-γ; NF-κB; PI3K; iNOS; PAMPs; CD36; α-synuclein; MAPKs; IL-1β; IL-6; Microglia; TLR1; ROS; TLR7; TLR4; CD44; TLR3; ERK; TLR2; NADPH; NO; THP-1; FcγRs; COX-2; PHOX; CNS; PLD2; IκB; TLR2/1; WT; BV-2; EP2; MMPs; cPLA2; IKK; AKT; Inflammation; NAC; P2×7R; PD; TNF-α; MHCII; Mac-1; MPTP; CD68; TLRs; Parkinson’s disease
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2016.11.002

•Described the characters for α-synuclein induced microglial activation in detail.•Summarized the pathways associated with α-synuclein induced microglial activation.•Collected the receptors or signal modules in α-synuclein induced microglial activation.•Discussed phagocytosis and migration in α-synuclein induced microglial activation. Parkinson’s disease (PD) is characterized by α-synuclein accumulation, dopaminergic neuron loss and inflammation. α-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-α), interleukin-1-β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ), 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 α-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 α-synuclein-activated microglia, with particular emphasis on the signaling cascades involved in this process.