ArticleThe Journal of clinical investigation2014
Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 78 citations in OpenAlex.
- DKK2 contributes to context discrimination and adult hippocampal neurogenesis by suppressing Wnt/PCP signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Gain-of-function PPM1D mutations attenuate ischemic stroke.Cell death and differentiation · 2025Article
- KDM3A controls postnatal hippocampal neurogenesis via dual regulation of the Wnt/β-catenin signaling pathway.Cell death and differentiation · 2025Article
- Targeting gut microbiota as a therapeutic approach for neurodegenerative diseases.Neuroprotection (Chichester, England) · 2025Article
- Therapeutic modulation of neurogenesis to improve hippocampal plasticity and cognition in aging and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- ErbB4 deficiency exacerbates olfactory dysfunction in an early-stage Alzheimer's disease mouse model.Acta pharmacologica Sinica · 2024Article
- Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases.Journal of translational medicine · 2024Review
- Article
- JUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer's disease.Nature communications · 2023Article
- Article
- From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer's and Parkinson's diseases.Neural regeneration research · 2022Review
- The role of serine/threonine phosphatases in human development: Evidence from congenital disorders.Frontiers in cell and developmental biology · 2022Review
- Activation of Wnt/Beta-Catenin Signaling Pathway as a Promising Therapeutic Candidate for Cerebral Ischemia/Reperfusion Injury.Frontiers in pharmacology · 2022Review
- PP2Cδ Controls the Differentiation and Function of Dendritic Cells Through Regulating the NSD2/mTORC2/ACLY Pathway.Frontiers in immunology · 2021Article
- Transcriptional regulation of adult neural stem/progenitor cells: tales from the subventricular zone.Neural regeneration research · 2020Review
- Neuronal changes and cognitive deficits in a multi-hit rat model following cumulative impact of early life stressors.Biology open · 2020Article
- Review
- Review
- Parkinson's disease, aging and adult neurogenesis: Wnt/β-catenin signalling as the key to unlock the mystery of endogenous brain repair.Aging cell · 2020Review
- Restoring Wnt/β-catenin signaling is a promising therapeutic strategy for Alzheimer's disease.Molecular brain · 2019Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The number of newly formed neurons declines rapidly during aging, and this decrease in neurogenesis is associated with decreased function of neural stem/progenitor cells (NPCs). Here, we determined that a WIP1-dependent pathway regulates NPC differentiation and contributes to the age-associated decline of neurogenesis. Specifically, we found that WIP1 is expressed in NPCs of the mouse subventricular zone (SVZ) and aged animals with genetically enhanced WIP1 expression exhibited higher NPC numbers and neuronal differentiation compared with aged WT animals. Additionally, augmenting WIP1 expression in aged animals markedly improved neuron formation and rescued a functional defect in fine odor discrimination in aged mice. We identified the WNT signaling pathway inhibitor DKK3 as a key downstream target of WIP1 and found that expression of DKK3 in the SVZ is restricted to NPCs. Using murine reporter strains, we determined that DKK3 inhibits neuroblast formation by suppressing WNT signaling and Dkk3 deletion or pharmacological activation of the WNT pathway improved neuron formation and olfactory function in aged mice. We propose that WIP1 controls DKK3-dependent inhibition of neuronal differentiation during aging and suggest that regulating WIP1 levels could prevent certain aspects of functional decline of the aging brain.
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Registered trials
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.