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Cited by 569Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease

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Singh, Deepali·2022·Journal of Neuroinflammation
DOI 10.1186/s12974-022-02565-0PMC PMC9382837
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Abstract

Neuroinflammation is instigated by the misfiring of immune cells in the central nervous system (CNS) involving microglia and astrocytes as key cell-types. Neuroinflammation is a consequence of CNS injury, infection, toxicity, or autoimmunity. It is favorable as well as a detrimental process for neurodevelopment and associated processes. Transient activation of inflammatory response involving release of cytokines and growth factors positively affects the development and post-injury tissue. However, chronic or uncontrolled inflammatory responses may lead to various neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, and multiple sclerosis. These diseases have variable clinical and pathological features, but are underlaid by the aggregation of misfolded proteins with a cytotoxic effect. Notably, abnormal activation of glial cells could mediate neuroinflammation, leading to the neurodegenerative condition. Microglia, a type of glial cell, a resident immune cell, form the forefront defense of the CNS immune system. Dysfunctional microglia and astrocyte, a different kind of glial cell with homeostatic function, impairs the protein aggregate (amyloid-beta plaque) clearance in AD. Studies have shown that microglia and astrocytes undergo alterations in their genetic profile, cellular and molecular responses, and thus promote dysfunctional immune cross-talk in AD. Hence, targeting microglia and astrocytes-driven molecular pathways could resolve the particular layers of neuroinflammation and set a reliable therapeutic intervention in AD progression.

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  • Sensitization with IL-1α + TNF-α + C1q recapitulates microglial activation and is reported to enhance GFAP protein levels and astrocyte neurotoxicity.

    “This sensitization intends to recapitulate that caused by microglial activation, a current condition in AD [70,71], reported to enhance GFAP protein levels and astrocyte neurotoxicity [44].”

    From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [70]

    In “Dysfunctional immune cross-talk cause neuroinflammation” (page unavailable), the review says activated microglia secrete IL-1α, TNF and C1q, inducing neurotoxic A1 astrocytes. “The role of astrocytes in neuroinflammation” (page unavailable) says reactive astrocytes have increased GFAP expression, but does not report that sensitization with this cytokine combination increases GFAP protein levels. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Microglia play a pivotal role by releasing factors such as TNF-α, IL-1β, and C1q, which trigger astrogliosis.

    “Microglia play a pivotal role by releasing factors such as tumor necrosis factor–α (TNF-α), interleukin-1β (IL-1β), and complement component 1q (C1q), which trigger astrogliosis (9, 15, 16).”

    From Varicose projection astrocytes: Conserved reactive cells in brain pathology (2026) · cites this paper as [16]

    In “Dysfunctional immune cross-talk cause neuroinflammation” (page not provided), the paper says activated microglia induce reactive A1 astrocytes by secreting IL-1α, TNF, and C1q. The claim matches the microglia-to-astrocyte effect and two factors, but substitutes IL-1β for IL-1α in the factor combination the paper identifies. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Glial cells are the primary cells involved in neuroinflammation and neurodegeneration.

    “As we have discussed above, glial cells are the primary cells involved in neuroinflammation and neurodegeneration. Their crucial function in the development and progression of neurodegenerative diseases has also been elaborated in many reviews in the past year.275,468,469”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [469]

  • Microglial activation is a current condition in AD.

    “a current condition in AD [70,71]”

    From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [70]

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Cited by

Sorted by citations

Authors
Singh, D.
Affiliations
National Brain Research Centre (IN)
Corresponding author
Singh, Deepali
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2022-08-17
Volume
19
Issue
1
Pages
206-206
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-022-02565-0
PMC
PMC9382837
OpenAlex
W4292320039
Cited by
569
References
47
Citations by year
2026: 152 · 2025: 225 · 2024: 127 · 2023: 60 · 2022: 5
FWCI
10.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Indian Council of Medical Research (5/3/8/58/ITR-F/2020)
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
neuroinflammation, Alzheimer's disease, microglia, astrocytes, glial cells, amyloid-beta clearance, protein aggregation, neurodegenerative diseases, cytokines, therapeutic target
MeSH terms
Neuroinflammatory Diseases, Alzheimer Disease, Astrocytes, Humans, Microglia

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