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Cited by 236Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Microglia and Alzheimer’s Disease

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Merighi, Stefania, Nigro, Manuela, Travagli, Alessia, Gessi, Stefania·2022·International Journal of Molecular Sciences
DOI 10.3390/ijms232112990PMC PMC9657945
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Abstract

There is a huge need for novel therapeutic and preventative approaches to Alzheimer’s disease (AD) and neuroinflammation seems to be one of the most fascinating solutions. The primary cell type that performs immunosurveillance and helps clear out unwanted chemicals from the brain is the microglia. Microglia work to reestablish efficiency and stop further degeneration in the early stages of AD but mainly fail in the illness’s later phases. This may be caused by a number of reasons, e.g., a protracted exposure to cytokines that induce inflammation and an inappropriate accumulation of amyloid beta (Aβ) peptide. Extracellular amyloid and/or intraneuronal phosphorylated tau in AD can both activate microglia. The activation of TLRs and scavenger receptors, inducing the activation of numerous inflammatory pathways, including the NF-kB, JAK-STAT, and NLRP3 inflammasome, facilitates microglial phagocytosis and activation in response to these mediators. Aβ/tau are taken up by microglia, and their removal from the extracellular space can also have protective effects, but if the illness worsens, an environment that is constantly inflamed and overexposed to an oxidative environment might encourage continuous microglial activation, which can lead to neuroinflammation, oxidative stress, iron overload, and neurotoxicity. The complexity and diversity of the roles that microglia play in health and disease necessitate the urgent development of new biomarkers that identify the activity of different microglia. It is imperative to comprehend the intricate mechanisms that result in microglial impairment to develop new immunomodulating therapies that primarily attempt to recover the physiological role of microglia, allowing them to carry out their core function of brain protection.

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Authors
Merighi, S., Nigro, M., Travagli, A., & Gessi, S.
Affiliations
University of Ferrara (IT)
Corresponding author
Merighi, Stefania
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2022-10-27
Volume
23
Issue
21
Pages
12990
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms232112990
PMC
PMC9657945
OpenAlex
W4307358100
Cited by
236
References
165
Citations by year
2026: 58 · 2025: 88 · 2024: 67 · 2023: 22 · 2022: 1
FWCI
4.61
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by)
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
microglia, Alzheimer's disease, neuroinflammation, amyloid-beta, tau phosphorylation, Toll-like receptors, scavenger receptors, NLRP3 inflammasome, NF-κB signaling, JAK/STAT signaling, oxidative stress, iron overload, neurotoxicity, microglial activation, immunomodulatory therapy, biomarkers
MeSH terms
Alzheimer Disease, Humans, Cytokines, Amyloid beta-Peptides, Microglia, Inflammasomes

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