ArticleEMBO molecular medicine2023
Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Deep brain stimulation of the nucleus basalis of Meynert in neurodegenerative diseases with cognitive impairment: An update on evidence and mechanisms.Neural regeneration research · 2026Article
- Soluble TREM1 Contributes to Aging-Related Neurodegeneration via ROBO2/ERK Pathway.Molecular neurobiology · 2026Article
- Inhibition of p38 MAPK after repetitive mTBI ameliorates immune signaling and functional deficits.Acta neuropathologica communications · 2026Article
- Therapeutic Approaches Interfering with Nuclear Localization Signals: An Emerging Strategy for CNS-Related Diseases.Current neuropharmacology · 2026Review
- MAPK3 as a ferroptosis driver in excitatory neurons in Alzheimer's disease: from genetic causal inference toFrontiers in aging neuroscience · 2026Article
- Article
- αPharmaceuticals (Basel, Switzerland) · 2025Review
- Opposing roles for GSK3β and ERK1-dependent phosphorylation of huntingtin during neuronal dysfunction and cell death in Huntington's disease.Cell death & disease · 2025Article
- Reduced Cacna1c Expression Produces Anhedonic Reactions to Palatable Sucrose in Rats: No Interactions With Juvenile or Adult Stress.Genes, brain, and behavior · 2025Article
- Further In Vitro and Ex Vivo Pharmacological and Kinetic Characterizations of CCF219B: A Positive Allosteric Modulator of the αPharmaceuticals (Basel, Switzerland) · 2025Article
- Urolithin A alleviates schizophrenic-like behaviors and cognitive impairment in rats through modulation of neuroinflammation, neurogenesis, and synaptic plasticity.Scientific reports · 2025Article
- Oxytocin Protects PC12 Cells Against β-Amyloid-Induced Cell Injury.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Mice with 16p11.2 Deletion and Duplication Show Alterations in Biological Processes Associated with White Matter.International journal of molecular sciences · 2025Article
- Innovations in Alzheimer's disease diagnostic technologies: clinical prospects of novel biomarkers, multimodal integration, and non-invasive detection.Frontiers in neurology · 2025Review
- Modulating voltage-gated sodium channels to enhance differentiation and sensitize glioblastoma cells to chemotherapy.Cell communication and signaling : CCS · 2024Article
- Understanding copy number variations through their genes: a molecular view on 16p11.2 deletion and duplication syndromes.Frontiers in pharmacology · 2024Review
- Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2.EMBO molecular medicine · 2023Article
Corrections and comments
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Authors and funding
25 authors at 9 institutions in 2 countries.
Funding
Abstract
Cell signaling is central to neuronal activity and its dysregulation may lead to neurodegeneration and cognitive decline. Here, we show that selective genetic potentiation of neuronal ERK signaling prevents cell death in vitro and in vivo in the mouse brain, while attenuation of ERK signaling does the opposite. This neuroprotective effect mediated by an enhanced nuclear ERK activity can also be induced by the novel cell penetrating peptide RB5. In vitro administration of RB5 disrupts the preferential interaction of ERK1 MAP kinase with importinα1/KPNA2 over ERK2, facilitates ERK1/2 nuclear translocation, and enhances global ERK activity. Importantly, RB5 treatment in vivo promotes neuroprotection in mouse models of Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) disease, and enhances ERK signaling in a human cellular model of HD. Additionally, RB5-mediated potentiation of ERK nuclear signaling facilitates synaptic plasticity, enhances cognition in healthy rodents, and rescues cognitive impairments in AD and HD models. The reported molecular mechanism shared across multiple neurodegenerative disorders reveals a potential new therapeutic target approach based on the modulation of KPNA2-ERK1/2 interactions.
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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.