Cited by 159Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Interleukin-34 Selectively Enhances the Neuroprotective Effects of Microglia to Attenuate Oligomeric Amyloid-β Neurotoxicity

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Mizuno, Tetsuya, Doi, Yukiko, Mizoguchi, Hiroyuki, Jin, Shijie, Noda, Mariko, Sonobe, Yoshifumi, Takeuchi, Hideyuki, Suzumura, Akio·2011·The American Journal of Pathology

Abstract

Microglia, macrophage-like resident immune cells in the brain, possess both neurotoxic and neuroprotective properties and have a critical role in the development of Alzheimer's disease (AD). We examined the function of Interleukin-34 (IL-34), a newly discovered cytokine, on microglia because it reportedly induces proliferation of monocytes and macrophages. We observed that the neuronal cells primarily produce IL-34 and that microglia express its receptor, colony-stimulating factor 1 receptor. IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-β (oAβ), which mediates synaptic dysfunction and neuronal damage in AD. IL-34 increased the expression of insulin-degrading enzyme, aiding the clearance of oAβ, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules. Consequently, microglia treated with IL-34 attenuated oAβ neurotoxicity in primary neuron-microglia co-cultures. In vivo, intracerebroventricular administration of IL-34 ameliorated impairment of associative learning and reduced oAβ levels through up-regulation of insulin-degrading enzyme and heme oxygenase-1 in an APP/PS1 transgenic mouse model of AD. These findings support the idea that enhancement of the neuroprotective property of microglia by IL-34 may be an effective approach against oAβ neurotoxicity in AD.

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Crossref · 10.1016/j.ajpath.2011.06.011

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  • Interleukins such as IL-18, IL-34, IL-4, IL-10, IL-13, and others have been reported as either up- or downregulated in patient brain tissue, CSF or blood in AD and related tauopathies.

    “Interleukins such as IL-18, IL-34, IL-4, IL-10 IL-13, and others have been reported as either up or downregulated in patient brain tissue, CSF or blood [92, 103, 167].”

    From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [167]

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Authors
Mizuno, T., Doi, Y., Mizoguchi, H., Jin, S., Noda, M., Sonobe, Y., Takeuchi, H., & Suzumura, A.
Affiliations
Research Institute of Environmental Medicine, Nagoya University (JP)
Corresponding author
Mizuno, Tetsuya
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2011-10
Volume
179
Issue
4
Pages
2016-2027
ISSN
0002-9440 (ISSN-L)
OpenAlex
W2093493917
Cited by
159
References
38
Citations by year
2026: 10 · 2025: 10 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 7 · 2017: 11 · 2016: 9 · 2015: 7 · 2014: 7 · 2013: 12 · 2012: 12
FWCI
5.65
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • National Institute of Biomedical Innovation
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
IL-34, microglia, amyloid-beta oligomers, Alzheimer's disease, neuroprotection, amyloid-beta clearance, insulin-degrading enzyme, heme oxygenase-1, oxidative stress, colony-stimulating factor 1 receptor, associative learning, APP/PS1 mice, neuroinflammation
MeSH terms
Alzheimer Disease, Animals, Antioxidants, Disease Models, Animal, Humans, Injections, Intraventricular, Insulysin, Interleukins, Learning, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Up-Regulation, Amyloid beta-Peptides, Microglia, Neuroprotective Agents, Coculture Techniques, Protein Structure, Quaternary, Cell Proliferation, Mice, Heme Oxygenase-1

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