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

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Abstract

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.

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Journal

Journal ID (iso-abbrev): Toxicol. Lett.

Title: Toxicology letters

Publisher: Elsevier BV

ISSN (Electronic): 1879-3169

ISSN (Print): 0378-4274

Publication date (Electronic): Jan 04 2017

Volume: 265

Affiliations

[1 ] State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

[2 ] State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: yuanyuhe@imm.ac.cn.

[3 ] State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Hunan University of Chinese Medicine, Changsha, 410208, China. Electronic address: chennh@imm.ac.cn.

Article

Publisher Item ID: S0378-4274(16)33295-7

DOI: 10.1016/j.toxlet.2016.11.002

PubMed ID: 27865851

SO-VID: 029d50b9-bd8d-4e57-97c6-0aae101b7bd7

History

Keywords: Inflammation,Microglia,Parkinson’s disease,α-synuclein

Data availability:

Keywords: Inflammation, Microglia, Parkinson’s disease, α-synuclein

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