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.
|Original language||English (US)|
|Title of host publication||Inflammation in Parkinson's Disease: Scientific and Clinical Aspects|
|Publisher||Springer International Publishing|
|Number of pages||22|
|ISBN (Print)||9783319080468, 3319080458, 9783319080451|
|State||Published - May 1 2014|
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