Abstract
Microglia-mediated neuroinflammation is a common feature of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Microglia can be categorized into two opposite types: classical (M1) or alternative (M2), though there’s a continuum of different intermediate phenotypes between M1 and M2, and microglia can transit from one phenotype to another. M1 microglia release inflammatory mediators and induce inflammation and neurotoxicity, while M2 microglia release anti-inflammatory mediators and induce anti-inflammatory and neuroprotectivity. Microglia-mediated neuroinflammation is considered as a double-edged sword, performing both harmful and helpful effects in neurodegenerative diseases. Previous studies showed that balancing microglia M1/M2 polarization had a promising therapeutic prospect in neurodegenerative diseases. We suggest that shifting microglia from M1 to M2 may be significant and we focus on the modulation of microglia polarization from M1 to M2, especially by important signal pathways, in neurodegenerative diseases.
Highlights
Neurodegenerative diseases, a leading cause of morbidity and disability, are attracting increasing attention as the considerable impact on society (Stephenson et al, 2018)
We briefly introduced the function and phenotype of microglia and focused on the role and polarization regulation of microglia in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), to probe into potential therapeutic strategies for neurodegenerative diseases
The modulators in microglia polarization from M1 to M2 can be divided into several categories, including transcription factors, receptors, cytokines, ion channels, bioactive compounds, and drugs (Supplementary Table 1), most of which are related to several important signal pathways (Figure 2)
Summary
Neurodegenerative diseases, a leading cause of morbidity and disability, are attracting increasing attention as the considerable impact on society (Stephenson et al, 2018). Promoting microglia polarization shift from M1 to M2 phenotype may be a more prospective strategy in the therapy of neurodegenerative diseases such as AD, PD, ALS, and MS (Wen et al, 2017; Zhang B. et al, 2018).
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