ArticleAging cell2022
p38α-MAPK-deficient myeloid cells ameliorate symptoms and pathology of APP-transgenic Alzheimer's disease mice.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 30 citations in OpenAlex.
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- Selective vulnerability of the aging cholinergic system to amyloid pathology revealed by induced APP overexpression.Journal of neuroinflammation · 2026Article
- Deciphering the Multi-Target Therapeutic Mechanisms of Traditional Chinese Medicine Against Alzheimer's Disease: A Network Pharmacology Perspective.Drug design, development and therapy · 2026Review
- Cordycepin Mitigates Sepsis-Associated Encephalopathy by Promoting Microglial M2 Polarization via the IL-17a/IL-17RA/NF-κB Axis.Molecular neurobiology · 2025Article
- Intestinal epithelial Dicer1 regulates gut microbiome and Alzheimer's pathology in App-knock-in mice.Alzheimer's research & therapy · 2025Article
- Metabolomics and network analysis reveal the mechanism of Salvia miltiorrhiza bunge extract in ameliorating cognitive dysfunction in sleep-deprived rats.Scientific reports · 2025Article
- Exploring the causal relationship and molecular mechanisms between Methyl-4-hydroxybenzoic acid (MEP) and Alzheimer's disease: a mendelian randomization, multi-omics, and network toxicology approach.Toxicology research · 2025Article
- Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases.Expert reviews in molecular medicine · 2025Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Fluorine-18-Labeled Positron Emission Tomography Probe Targeting Activated p38α: Design, Synthesis, and In Vivo Evaluation in Rodents.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Investigating the impact of aspartame on Alzheimer's disease through network toxicology and molecular docking.Frontiers in nutrition · 2025Article
- GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14.Cellular & molecular immunology · 2024Article
- Downregulation of miR-181c-5p in Alzheimer's disease weakens the response of microglia to Aβ phagocytosis.Scientific reports · 2024Article
- Inflammation and Brain Structure in Alzheimer's Disease and Other Neurodegenerative Disorders: a Mendelian Randomization Study.Molecular neurobiology · 2024Article
- Study on the Pharmacological Mechanism of Icariin for the Treatment of Alzheimer's Disease Based on Network Pharmacology and Molecular Docking Techniques.Metabolites · 2023Article
- TAK1 Improves Cognitive Function via Suppressing RIPK1-Driven Neuronal Apoptosis and Necroptosis in Rats with Chronic Hypertension.Aging and disease · 2023Article
- Article
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9 authors at 1 institution in 1 country.
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Abstract
Alzheimer's disease (AD), the most common cause of dementia in the elderly, is pathologically characterized by extracellular deposition of amyloid-β peptides (Aβ) and microglia-dominated inflammatory activation in the brain. p38α-MAPK is activated in both neurons and microglia. How p38α-MAPK in microglia contributes to AD pathogenesis remains unclear. In this study, we conditionally knocked out p38α-MAPK in all myeloid cells or specifically in microglia of APP-transgenic mice, and examined animals for AD-associated pathologies (i.e., cognitive deficits, Aβ pathology, and neuroinflammation) and individual microglia for their inflammatory activation and Aβ internalization at different disease stages (e.g., at 4 and 9 months of age). Our experiments showed that p38α-MAPK-deficient myeloid cells were more effective than p38α-MAPK-deficient microglia in reducing cerebral Aβ and neuronal impairment in APP-transgenic mice. Deficiency of p38α-MAPK in myeloid cells inhibited inflammatory activation of individual microglia at 4 months but enhanced it at 9 months. Inflammatory activation promoted microglial internalization of Aβ. Interestingly, p38α-MAPK-deficient myeloid cells reduced IL-17a-expressing CD4-positive lymphocytes in 9 but not 4-month-old APP-transgenic mice. By cross-breeding APP-transgenic mice with Il-17a-knockout mice, we observed that IL-17a deficiency potentially activated microglia and reduced Aβ deposition in the brain as shown in 9-month-old myeloid p38α-MAPK-deficient AD mice. Thus, p38α-MAPK deficiency in all myeloid cells, but not only in microglia, prevents AD progression. IL-17a-expressing lymphocytes may partially mediate the pathogenic role of p38α-MAPK in peripheral myeloid cells. Our study supports p38α-MAPK as a therapeutic target for AD patients.
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