Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases

Yu Tang, Weidong Le

Research output: Contribution to journalReview article

604 Scopus citations

Abstract

One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

Original languageEnglish (US)
Pages (from-to)1181-1194
Number of pages14
JournalMolecular Neurobiology
Volume53
Issue number2
DOIs
StatePublished - Mar 1 2016

Keywords

  • Alternative activation
  • Classical activation
  • M1/M2 switching
  • M2 microglia
  • Microglial phenotypes
  • Neurodegenerative diseases

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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