ArticleAging2020
TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer's disease mice.
Article in Aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 193 citations in OpenAlex.
- TREM2-Targeting peptide tracer for neuroinflammation PET imaging.European journal of nuclear medicine and molecular imaging · 2026Article
- Chasing the FoxO in Metabolic Disorders: Novel Considerations for Oxidative Stress, Programmed Cell Death, Wnt, and the Gut Microbiome.Antioxidants (Basel, Switzerland) · 2026Review
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- TREM2 in neurodegeneration and diseases.Molecular psychiatry · 2026Review
- The Biological Basis, Mechanisms of Action, and Optimization Strategies of Exosomes Derived from Mesenchymal Stem Cells for the Treatment of Alzheimer's Disease.Molecular neurobiology · 2026Review
- New Vistas for Withania somnifera in Signal Transduction of Inflammation and Aging.Pharmaceutical research · 2026Review
- Cholecalciferol (vitamin D3) is an agonist of the Alzheimer's disease-associated immune receptor TREM2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Alzheimer's Disease as a Disorder of Neuroimmune Dysregulation.Neurology international · 2026Review
- Investigating the protective and therapeutic potential of new generation antioxidant combinations in the brain: an experimental aging model.Biogerontology · 2026Article
- Soluble TREM2 Is Elevated in Pediatric Patients with Anti-NMDAR Encephalitis.Journal of clinical medicine · 2026Article
- The Immuno-Glial Connectome in Alzheimer's Disease: Integrating Central and Peripheral Inflammatory Networks.Cellular and molecular neurobiology · 2026Review
- Microglia-derived neuroinflammatory pathways in neuropathic pain.The Korean journal of pain · 2026Review
- Running out the clock: Circadian rhythm dysfunction in cognitive disease.International review of neurobiology · 2026Review
- Mechanisms of interaction between type 2 diabetes and psychological disorders and therapeutic interventions: a narrative review.Frontiers in medicine · 2026Review
- Ketogenic interventions enhance REM sleep in females and support memory in aged rats.Frontiers in aging neuroscience · 2026Article
- ZDWX-25, a dual DYRK1A/GSK3β inhibitor, attenuates tau hyperphosphorylation and neuroinflammation in acute mouse models.Frontiers in pharmacology · 2026Article
- Agitation, Alzheimer's disease, and autophagy: mechanistic insights into aging pathways, gut microbiome, and artificial intelligence.Frontiers in immunology · 2026Review
- Neuroinflammation in Alzheimer's disease-associated sensory dysfunction: mechanistic links, actionable targets and therapeutic strategies.Frontiers in aging neuroscience · 2026Review
- Gastrodia elata fermentation alleviates methamphetamine-induced neuroinflammation and anxiety- and depression-like behaviors by regulating the PI3K-AKT signaling pathway.Frontiers in medicine · 2026Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) has been shown with a neuroprotective function against inflammation and neuronal injury in Alzheimer's disease (AD). However, the TREM2 induced anti-inflammatory mechanism is still not well known. In this study it has been demonstrated that the expression of TREM2 was upregulated in hippocampus of 5xFAD mice, whereas TREM2 knock-out mediated by AAV significantly increased the levels of pro-inflammatory cytokines and aggravated cognitive defect. Additionally, FoxO3a, a downstream member of the PI3K/AKT pathway, could be activated by TREM2 defect via the PI3K/AKT signaling in 5xFAD mice. That suggests TREM2-induced protection is associated with the PI3K-FoxO3a axis. On the contrary, overexpression of TREM2 alleviated the LPS-induced inflammatory response and induced M2 phenotype microglia in vitro. This phenomenon can be abolished by applying the PI3K inhibitor LY294002, suggesting FoxO3a not only participates in TREM2-induced anti-inflammation response, but is also involved in regulating the phenotype of microglia. Taken together, our results show that the protective functions of TREM2, both in inflammatory response and cognitive impairment as well as in the decrease of M1 phenotype microglia, are related to PI3K/AKT/FoxO3a signaling pathway in AD mice.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.