Cited by 308Neuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and TreatmentsMultiple Sclerosis Research Studies

The identity and function of microglia in neurodegeneration

Song, Wilbur M., Colonna, Marco·2018·Nature Immunology

Abstract

The predominant type of immune cell in the brain is the microglia, a type of tissue-resident macrophage. In a variety of neurodegenerative settings, microglia alter their transcriptional profile, morphology and function in similar ways; thus, these activated cells have been called 'degeneration- or disease-associated microglia' (DAM). These activated microglia can perform different functions and exert both positive effects and negative effects in different mouse disease models. In humans, mutations in genes expressed in microglia are linked to various neurodegenerative diseases. Here we provide an overview of the common microglial response to neurodegeneration and key contributing pathways; delineate the multifaceted functions of activated microglia spanning various diseases; and discuss insights from the study of human disease-associated genes. We argue that strong evidence from both mouse models and human genetics causally links the function of activated microglia to neurodegeneration.

Integrity signals

Registry

Crossref · 10.1038/s41590-018-0212-1

Cites

178 of 178 references verified0 citation errors · 0 not checkable

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  • DAM phenotype has been proposed to represent a universal and intrinsic microglial response program to CNS disease, retained across neurodegenerative and non-neurodegenerative diseases.

    “The DAM phenotype has been proposed to represent a universal and intrinsic microglial response program to CNS disease, since it appears to be retained across a number of neurodegenerative and non-neurodegenerative diseases [74, 291]”
  • DAM-expressed factors such as apolipoprotein, CSF1, and secreted phosphoprotein 1 act as autocrine ligands on DAM-expressed receptors, sustaining and perpetuating neurodegenerative phenotype.

    “DAM-expressed factors, such as apolipoprotein, colony-stimulating factor 1 (CSF1) and secreted phosphoprotein 1, act as autocrine ligands on DAM-expressed receptors, together sustaining and perpetuating the neurodegenerative phenotype [291]”
  • Complement activation can exacerbate synaptic loss and contribute to memory loss and cognitive decline.

    “complement activation, which is important for microglial phagocytosis, can exacerbate synaptic loss [152, 284, 291] and contribute to memory loss and cognitive decline [75]”
  • Microglia are classified into M1 (classically activated) cells that secrete proinflammatory cytokines and M2 (alternatively activated) cells that promote tissue regeneration and repair.

    “Microglia are classified into two subtypes: classically activated (M1) cells, which secrete proinflammatory cytokines, and alternatively activated (M2) cells, which promote tissue regeneration and repair [9–12].”
  • Microgliosis is a known feature of AD.

    “Microgliosis is a known feature of AD [reviewed in (92, 93)]”

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Authors
Song, W. M., & Colonna, M.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Colonna, Marco
Venue
Nature Immunology
Published
2018-09-24
Volume
19
Issue
10
Pages
1048-1058
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2891888347
Cited by
308
References
178
Citations by year
2026: 21 · 2025: 28 · 2024: 37 · 2023: 49 · 2022: 53 · 2021: 42 · 2020: 42 · 2019: 33 · 2018: 3
FWCI
2.84
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
microglia, neurodegeneration, disease-associated microglia, microglial activation, tissue-resident macrophages, microglial morphology, neurodegenerative disease models, microglial function
MeSH terms
Animals, Humans, Microglia, Neurodegenerative Diseases

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