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Cited by 25Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Targeting Microglial Population Dynamics in Alzheimer’s Disease: Are We Ready for a Potential Impact on Immune Function?

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Martin-Estebane, Maria, Gomez-Nicola, Diego·2020·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2020.00149PMC PMC7289918
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Abstract

Alzheimer's disease (AD) is the most common form of dementia, affecting two-thirds of people with dementia in the world. To date, no disease-modifying treatments are available to stop or delay the progression of AD. This chronic neurodegenerative disease is dominated by a strong innate immune response, whereby microglia plays a central role as the main resident macrophage of the brain. Recent genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) located in microglial genes and associated with a delayed onset of AD, highlighting the important role of these cells on the onset and/or progression of the disease. These findings have increased the interest in targeting microglia-associated neuroinflammation as a potentially disease-modifying therapeutic approach for AD. In this review we provide an overview on the contribution of microglia to the pathophysiology of AD, focusing on the main regulatory pathways controlling microglial population dynamics during the neuroinflammatory response, such as the colony-stimulating factor 1 receptor (CSF1R), its ligands (the colony-stimulating factor 1 and interleukin 34) and the transcription factor PU.1. We also discuss the current therapeutic strategies targeting proliferation to modulate microglia-associated neuroinflammation and their potential impact on peripheral immune cell populations in the short and long-term. Understanding the effects of immunomodulatory approaches on microglia and other immune cell types might be critical for developing specific, effective, and safe therapies for neurodegenerative diseases.

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  • The beneficial effect of a therapeutic agent on microglia function in the brain might be accompanied by a dysregulation of other immune cells' function and other tissues/organs, such as bones and liver.

    “the beneficial effect of a therapeutic agent on microglia function in the brain might be accompanied by a dysregulation of other immune cells’ function and other tissues/organs, such as bones and liver [131]”

    From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [131]

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Cited by

Sorted by citations

Authors
Martin-Estebane, M., & Gomez-Nicola, D.
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2020-06-05
Volume
14
Pages
149-149
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2020.00149
PMC
PMC7289918
OpenAlex
W3033678788
Cited by
25
References
34
Citations by year
2026: 2 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 3
FWCI
1.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Medical Research Council
  • Fundación Alfonso Martin Escudero
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, microglia, neuroinflammation, CSF1R, colony-stimulating factor 1, IL-34, PU.1, microglial proliferation, disease-modifying therapy, peripheral immune cells, innate immunity, single nucleotide polymorphisms, immunomodulation

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