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Cited by 78Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease

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Hashioka, Sadayuki, Wu, Zhou, Klegeris, Andis·2021·Current Neuropharmacology
DOI 10.2174/1570159x18666201111104509PMC PMC8686312
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Abstract

The neuroinflammatory hypothesis of Alzheimer’s disease (AD) was proposed more than 30 years ago. The involvement of the two main types of glial cells microglia and astrocytes, in neuroinflammation, was suggested early on. In this review, we highlight that the exact contributions of reactive glia to AD pathogenesis remain difficult to define, likely due to the heterogeneity of glia populations and alterations in their activation states through the stages of AD progression. In the case of microglia, it is becoming apparent that both beneficially and adversely activated cell populations can be identified at various stages of AD, which could be selectively targeted to either limit their damaging actions or enhance beneficial functions. In the case of astrocytes, less information is available about potential subpopulations of reactive cells; it also remains elusive whether astrocytes contribute to the neuropathology of AD by mainly gaining neurotoxic functions or losing their ability to support neurons due to astrocyte damage. We identify L-type calcium channel blocker, nimodipine, as a candidate drug for AD, which potentially targets both astrocytes and microglia. It has already shown consistent beneficial effects in basic experimental and clinical studies. We also highlight the recent evidence linking peripheral inflammation and neuroinflammation. Several chronic systemic inflammatory diseases, such as obesity, type 2 diabetes mellitus, and periodontitis, can cause immune priming or adverse activation of glia, thus exacerbating neuroinflammation and increasing risk or facilitating the progression of AD. Therefore, reducing peripheral inflammation is a potentially effective strategy for lowering AD prevalence.

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Cited by

Sorted by citations

Authors
Hashioka, S., Wu, Z., & Klegeris, A.
Affiliations
  • Shimane University (JP)
  • Kyushu University (JP)
  • University of British Columbia, Okanagan Campus (CA)
Corresponding author
  • Hashioka, Sadayuki
  • Klegeris, Andis
ORCID
Venue
Current Neuropharmacology
Publisher
Bentham Science Publishers Ltd.
Published
2021-07
Volume
19
Issue
7
Pages
908-924
ISSN
1570-159X (ISSN-L)
DOI
10.2174/1570159x18666201111104509
PMC
PMC8686312
OpenAlex
W3101159832
Cited by
78
References
42
Citations by year
2026: 10 · 2025: 18 · 2024: 20 · 2023: 20 · 2022: 7 · 2021: 3
FWCI
2.85
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Current Neuropharmacology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
JSPS KAKENHI (19K08018, 16K11478)
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, neuroinflammation, microglia, astrocytes, reactive glia, glial heterogeneity, microglial activation states, astrocyte damage, peripheral inflammation, systemic inflammation, nimodipine, L-type calcium channel blockers, obesity, type 2 diabetes, periodontitis, immune priming
MeSH terms
Alzheimer Disease, Astrocytes, Diabetes Mellitus, Type 2, Humans, Inflammation, Neuroglia, Microglia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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