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Cited by 90Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsPhagocytosis and Immune Regulation

Metabolic regulation of microglial phagocytosis: Implications for Alzheimer's disease therapeutics

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Lepiarz-Raba, Izabela, Gbadamosi, Ismail, Florea, Roberta, Paolicelli, Rosa Chiara, Jawaid, Ali·2023·Translational Neurodegeneration
DOI 10.1186/s40035-023-00382-wPMC PMC10617244
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Abstract

Microglia, the resident immune cells of the brain, are increasingly implicated in the regulation of brain health and disease. Microglia perform multiple functions in the central nervous system, including surveillance, phagocytosis and release of a variety of soluble factors. Importantly, a majority of their functions are closely related to changes in their metabolism. This natural inter-dependency between core microglial properties and metabolism offers a unique opportunity to modulate microglial activities via nutritional or metabolic interventions. In this review, we examine the existing scientific literature to synthesize the hypothesis that microglial phagocytosis of amyloid beta (Aβ) aggregates in Alzheimer’s disease (AD) can be selectively enhanced via metabolic interventions. We first review the basics of microglial metabolism and the effects of common metabolites, such as glucose, lipids, ketone bodies, glutamine, pyruvate and lactate, on microglial inflammatory and phagocytic properties. Next, we examine the evidence for dysregulation of microglial metabolism in AD. This is followed by a review of in vivo studies on metabolic manipulation of microglial functions to ascertain their therapeutic potential in AD. Finally, we discuss the effects of metabolic factors on microglial phagocytosis of healthy synapses, a pathological process that also contributes to the progression of AD. We conclude by enlisting the current challenges that need to be addressed before strategies to harness microglial phagocytosis to clear pathological protein deposits in AD and other neurodegenerative disorders can be widely adopted.

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Cited by

Sorted by citations

Authors
Lepiarz-Raba, I., Gbadamosi, I., Florea, R., Paolicelli, R. C., & Jawaid, A.
Affiliations
  • Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
  • ETH Zurich (CH)
  • University of Lausanne (CH)
Corresponding author
Jawaid, Ali
ORCID
Venue
Translational Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2023-10-31
Volume
12
Issue
1
Pages
48-48
ISSN
2047-9158 (ISSN-L)
DOI
10.1186/s40035-023-00382-w
PMC
PMC10617244
OpenAlex
W4388082182
Cited by
90
References
25
Citations by year
2026: 43 · 2025: 32 · 2024: 15
FWCI
2.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRIS (submittedVersion, cc-by)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (197940, 310030)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
microglial metabolism, microglial phagocytosis, Alzheimer's disease, amyloid-beta clearance, metabolic intervention, ketone bodies, glucose metabolism, glutamine, pyruvate, lactate, microglial inflammation, neurodegenerative diseases, therapeutic target
MeSH terms
Alzheimer Disease, Brain, Humans, Phagocytosis, Amyloid beta-Peptides, Microglia

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