ArticleActa neuropathologica2020
Reduction of advanced tau-mediated memory deficits by the MAP kinase p38γ.
Article in Acta neuropathologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Tau T205 phosphorylation modulates engram cell recruitment and remote memory in mice.Nature communications · 2026Article
- Age-dependent elevation of Nr4a1 attenuates PI3K/AKT/GSK3β pathway and mediates tau hyperphosphorylation and cognitive impairments.Journal of advanced research · 2026Article
- Genetic medicines for epilepsy: unlocking new avenues for seizure control.Frontiers in bioengineering and biotechnology · 2026Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Article
- The promise of gene therapy in common types of dementia.BioImpacts : BI · 2025Review
- Review
- Development of small-molecule Tau-SH3 interaction inhibitors that prevent amyloid-β toxicity and network hyperexcitability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD.Science translational medicine · 2023Article
- Article
- Treatment of epilepsy using a targeted p38γ kinase gene therapy.Science advances · 2022Article
- Loss of LAMP5 interneurons drives neuronal network dysfunction in Alzheimer's disease.Acta neuropathologica · 2022Article
- Tau target identification reveals NSF-dependent effects on AMPA receptor trafficking and memory formation.The EMBO journal · 2022Article
- Alzheimer's disease: Ablating single master site abolishes tau hyperphosphorylation.Science advances · 2022Article
- Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders.Neurological research and practice · 2022Review
- Tau Acts in Concert With Kinase/Phosphatase Underlying Synaptic Dysfunction.Frontiers in aging neuroscience · 2022Review
- Lipid Peroxidation Induced ApoE Receptor-Ligand Disruption as a Unifying Hypothesis Underlying Sporadic Alzheimer's Disease in Humans.Journal of Alzheimer's disease : JAD · 2022Article
- A novel dephosphorylation targeting chimera selectively promoting tau removal in tauopathies.Signal transduction and targeted therapy · 2021Article
- When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer's and Huntington's Disease.International journal of molecular sciences · 2021Review
- Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperphosphorylation of the neuronal tau protein contributes to Alzheimer's disease (AD) by promoting tau pathology and neuronal and cognitive deficits. In contrast, we have previously shown that site-specific tau phosphorylation can inhibit toxic signals induced by amyloid-β (Aβ) in mouse models. The post-synaptic mitogen-activated protein (MAP) kinase p38γ mediates this site-specific phosphorylation on tau at Threonine-205 (T205). Using a gene therapeutic approach, we draw on this neuroprotective mechanism to improve memory in two Aβ-dependent mouse models of AD at stages when advanced memory deficits are present. Increasing activity of post-synaptic kinase p38γ that targets T205 in tau reduced memory deficits in symptomatic Aβ-induced AD models. Reconstitution experiments with wildtype human tau or phosphorylation-deficient tauT205A showed that T205 modification is critical for downstream effects of p38γ that prevent memory impairment in APP-transgenic mice. Furthermore, genome editing of the T205 codon in the murine Mapt gene showed that this single side chain in endogenous tau critically modulates memory deficits in APP-transgenic Alzheimer's mice. Ablating the protective effect of p38γ activity by genetic p38γ deletion in a tau transgenic mouse model that expresses non-pathogenic tau rendered tau toxic and resulted in impaired memory function in the absence of human Aβ. Thus, we propose that modulating neuronal p38γ activity serves as an intrinsic tau-dependent therapeutic approach to augment compromised cognition in advanced dementia.
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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.