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Molecular Neurobiology

, Volume 53, Issue 2, pp 1181–1194 | Cite as

Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases

  • Yu Tang
  • Weidong Le
Article

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.

Keywords

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

Abbreviations

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

APP

Amyloid precursor protein

Arg1

Arginase 1

β-Amyloid

BDNF

Brain-derived neurotrophic factor

CD206

Mannose receptor

Chi3l3

Chitinase-3-Like-3

CNS

Central nervous system

DA

Dopaminergic

ECM

Extracellular matrix

FIZZ1

Found in inflammatory zone 1

IFN-γ

Interferon-γ

IGF-I

Insulin-like growth factor 1

IL

Interleukin

iNOS

Induced nitric oxide synthase

LBs

Lewy bodies

LPS

Lipopolysaccharide

MHC

Major histocompatibility complex

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

mSOD1

Mutated superoxide dismutase

NO

Nitric oxide

PD

Parkinson’s disease

PET

Positron emission tomography

PS1

Presenilin-1

RELM

Resistin-like molecules

ROS

Reactive oxygen species

SN

Substantia nigra

SRA

Scavenger receptors

TAM

Tumor-associated macrophages

TDP-43

TAR DNA-binding protein 43

TGF-β

Transforming growth factor-β

TLRs

Toll-like receptors

TNF-α

Tumor necrosis factor-α

TTBK

Tau-tubulin kinase

Notes

Acknowledgments

This work was supported by grants from the National Natural Sciences Foundation of China (No. 81171201) and the National Basic Research Program of China (No. 2011CB510003).

Conflict of Interest

The authors declare no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological SciencesChinese Academy of Sciences/Shanghai JiaoTong University School of MedicineShanghaiChina
  2. 2.Center for Translational Research of Neurology Disease1st Affiliated Hospital, Dalian Medical UniversityDalianChina

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