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“Good” and “Bad” Microglia in Parkinson’s Disease: An Understanding of Homeostatic Mechanisms in Immunomodulation

  • Yu Tang
  • Weidong Le
Chapter

Abstract

Extensive neuroinflammation in the midbrain is a hallmark of Parkinson’s disease (PD), and it is believed to contribute to the disease course and progression. Reactive microglia are a major component of neuroinflammatory machinery that can produce either detrimental effects or neuroprotective effects. Generally, microglia in the brain can present in two states, namely, “bad microglia” or “good microglia.” In this chapter, we will update the recent research results of the two distinctive pathogenic phenotypes of “bad” and “good” microglia in PD. For example, “bad” microglia can be induced by endogenous proteins such as α-synuclein and a variety of environmental cues, which eventually converge into the effectors including pro-inflammatory cytokines, reactive oxygen species (ROS) and superoxide, and especially nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The functions of “good” microglia are mainly involved in the transrepression through multiple receptors, anti-inflammatory cytokines, neuron-microglia cross-talk, and microRNAs that counteract with “bad” microglia by repressing pro-inflammatory cytokines, NF-κB, and other factors. Those mechanisms attributed by “bad” or “good” microglia are not in parallel pathways but in cross-talk with each other to amplify their effects. Notably, both “bad” microglia and “good” microglia are essential for maintaining the homeostasis of the central nervous system (CNS). Whereas in PD, the persistence of pro-inflammation in “bad” microglia or a failure in protective mechanisms in “good” microglia might lead to the uncontrolled and sustained inflammation, which can drive the chronic, progressive neurodegenerative process. Targeting microglia by switching their activation states in an optimal window might be a promising therapeutic strategy for the treatment of PD. A broad and in-depth investigation into the transition of “bad/good” microglia is much needed to achieve this goal.

Keywords

Experimental Autoimmune Encephalomyelitis Substantia Nigra NADPH Oxidase Microglial Activation Experimental Autoimmune Neuritis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Institute of Health Sciences, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  2. 2.The First Affiliated Hospital of Dalian Medical University, Translational Research Institutes of MedicineDalianChina

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