ArticleAging cell2021
YAP prevents premature senescence of astrocytes and cognitive decline of Alzheimer's disease through regulating CDK6 signaling.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 96 citations in OpenAlex.
- Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.Neural regeneration research · 2026Article
- Low-Sample Input miRNA Profiling in Extracellular Vesicles-Enriched Plasma Fractions from Older Adults With/out Cognitive Impairment.International journal of molecular sciences · 2026Article
- Article
- Andrographolide attenuates microglial senescence in Alzheimer's disease mice by suppressing the STAT3 signaling.iScience · 2026Article
- YAP1 Upregulates Cytoskeleton Regulator ARHGEF1 and Tissue Regeneration Factor NEDD9 in a Multiplex Proteomic Study.Neurology international · 2026Article
- Elevated TRIM25 Impairs Poly (ADP-ribose) Metabolism via PARG Degradation and Mediates Compression-Induced Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hippo-YAP/TAZ Signaling in Astrocytes and Microglia: Role in Neuroinflammation, Neurodegeneration and Glial Tumors.International journal of molecular sciences · 2026Review
- Review
- Xmu-mp-1 attenuates streptozotocin-induced neurotoxicity in SH-SY5Y cells: potential role of Hippo pathway modulation.Molecular biology reports · 2026Article
- Stage-Dependent Function of Astrocytes in Alzheimer's Disease: A Review.Neuroscience insights · 2026Review
- Transcriptional regulation in cardiovascular aging.Frontiers in cardiovascular medicine · 2026Review
- Ammonia reduces glutamine synthetase expression in astrocytes via activation of Hippo-YAP signaling pathways.Communications biology · 2025Article
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- Upregulation of adenosine AMolecular psychiatry · 2025Article
- cGAS-STING signaling in brain aging and neurodegeneration: molecular links and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Integrated Multi-Omics Analysis and Cross-Model Validation Reveal Mitochondrial Signatures in Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Article
- The Hippo signaling pathway as a therapeutic target in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Oxidative stress activates YAP/TEAD1/NCOA4 axis to promote ferroptosis of endplate chondrocytes and aggravate intervertebral disc degeneration.Journal of orthopaedic translation · 2025Article
- Proinflammatory transcriptomic and kinomic alterations in astrocytes derived from patients with familial Alzheimer's disease.Brain, behavior, & immunity - health · 2025Article
- Astrocytic YAP prevents the glutamate neurotoxicity by upregulation of EAAT2 expression and promotes the gain of stemness in astrocytes in ischemic stroke mice.Cell death & disease · 2025Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescent astrocytes accumulate with aging and contribute to brain dysfunction and diseases such as Alzheimer's disease (AD), however, the mechanisms underlying the senescence of astrocytes during aging remain unclear. In the present study, we found that Yes-associated Protein (YAP) was downregulated and inactivated in hippocampal astrocytes of aging mice and AD model mice, as well as in D-galactose and paraquat-induced senescent astrocytes, in a Hippo pathway-dependent manner. Conditional knockout of YAP in astrocytes significantly promoted premature senescence of astrocytes, including reduction of cell proliferation, hypertrophic morphology, increase in senescence-associated β-galactosidase activity, and upregulation of several senescence-associated genes such as p16, p53 and NF-κB, and downregulation of Lamin B1. Further exploration of the underlying mechanism revealed that the expression of cyclin-dependent kinase 6 (CDK6) was decreased in YAP knockout astrocytes in vivo and in vitro, and ectopic overexpression of CDK6 partially rescued YAP knockout-induced senescence of astrocytes. Finally, activation of YAP signaling by XMU-MP-1 (an inhibitor of Hippo kinase MST1/2) partially rescued the senescence of astrocytes and improved the cognitive function of AD model mice and aging mice. Taken together, our studies identified unrecognized functions of YAP-CDK6 pathway in preventing astrocytic senescence in vitro and in vivo, which may provide further insights and new targets for delaying brain aging and aging-related neurodegenerative diseases such as AD.
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