Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation
Open accessAbstract
Microglia are integral mediators of innate immunity within the mammalian central nervous system. Typical microglial responses are transient, intending to restore homeostasis by orchestrating the removal of pathogens and debris and the regeneration of damaged neurons. However, prolonged and persistent microglial activation can drive chronic neuroinflammation and is associated with neurodegenerative disease. Recent evidence has revealed that abnormalities in microglial signaling pathways involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) may contribute to altered microglial activity and exacerbated neuroimmune responses. In this scoping review, the known and suspected roles of PI3K-AKT signaling in microglia, both during health and pathological states, will be examined, and the key microglial receptors that induce PI3K-AKT signaling in microglia will be described. Since aberrant signaling is correlated with neurodegenerative disease onset, the relationship between maladapted PI3K-AKT signaling and the development of neurodegenerative disease will also be explored. Finally, studies in which microglial PI3K-AKT signaling has been modulated will be highlighted, as this may prove to be a promising therapeutic approach for the future treatment of a range of neuroinflammatory conditions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PI3K/AKT signaling has been suggested to regulate many of the processes and pathways linked to microglial activation in AD.
“The downstream signaling that coordinates DAM acquisition has remained poorly described, although it has been suggested that PI3K/AKT signaling can regulate many of the processes and pathways linked to microglial activation in AD (Chu et al., 2021).”
From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Chu et al., 2021
Activation of TLR4 results in tyrosine phosphorylation of MyD88, which can recruit p85 and activate PI3K/Akt signaling.
“Activation of TLR4 results in the tyrosine phosphorylation of its cytosolic adaptor protein myeloid differentiation primary response 88 (MyD88), which can recruit the p85 subunit of PI3K and activate PI3K/Akt signaling [116].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [116]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 196 · Cited by 152
- Authors
- Chu, E., Mychasiuk, R., Hibbs, M. L., & Semple, B. D.
- Affiliations
- Monash University (AU)
- The Alfred Hospital (AU)
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Hibbs, Margaret L.
- Semple, Bridgette D.
- Venue
- Journal of Neuroinflammation
- Published
- 2021-11-27
- Volume
- 18
- Issue
- 1
- Pages
- 276-276
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC8627624
- OpenAlex
- W3217040496
- Cited by
- 152
- References
- 196
- Citations by year
- 2026: 36 · 2025: 37 · 2024: 45 · 2023: 25 · 2022: 9
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- 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)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- department of education, skills and employment, australian government (Research Training Stipend)
- capstone editing
- national health and medical research council
- central clinical school, monash university
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, phosphatidylinositol 3-kinase, Akt signaling, chronic neuroinflammation, microglial activation, neurodegenerative diseases, microglial receptors, neuroimmune response
- MeSH terms
- Neuroinflammatory Diseases, Animals, Brain, Humans, Signal Transduction, Microglia, Phosphatidylinositol 3-Kinase
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 ›
Are you an author, or do you see a problem with this page? Request a review
