ArticleAging cell2020
Tau inhibits PKA by nuclear proteasome-dependent PKAR2α elevation with suppressed CREB/GluA1 phosphorylation.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- A Virus-Like-Particle-Based Conjugate Vaccine Targeting the Microtubule Binding Region of Tau Protein.ACS omega · 2026Article
- Selective knockout of PKA regulatory subunits reveal opposite catalytic and metabolic consequences with implications for Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- HDAC7 acts as an astrocytic mediator of Aβ pathology that directly engages IKK to drive astrocyte neurotoxicity and neurodegeneration in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Upregulated astrocytic HDAC7 induces depression-like disorders via deacetylating PINK1 and inhibiting mitophagy.Journal of neuroinflammation · 2025Article
- Hippocampal Neurogenesis in Alzheimer's Disease: Multimodal Therapeutics and the Neurogenic Impairment Index Framework.International journal of molecular sciences · 2025Review
- Upregulated astrocyte HDAC7 induces Alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis.Molecular neurodegeneration · 2025Article
- Interactions Between the Ubiquitin-Proteasome System, Nrf2, and the Cannabinoidome as Protective Strategies to Combat Neurodegeneration: Review on Experimental Evidence.Neurotoxicity research · 2024Review
- Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer's Disease.Biomolecules · 2023Review
- Quercetagitrin Inhibits Tau Accumulation and Reverses Neuroinflammation and Cognitive Deficits in P301S-Tau Transgenic Mice.Molecules (Basel, Switzerland) · 2023Article
- Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation.Molecular neurodegeneration · 2023Article
- The Role of Traditional Chinese Medicine Natural Products in β-Amyloid Deposition and Tau Protein Hyperphosphorylation in Alzheimer's Disease.Drug design, development and therapy · 2023Review
- De novo mutations within metabolism networks of amino acid/protein/energy in Chinese autistic children with intellectual disability.Human genomics · 2022Article
- Tau Toxicity in Neurodegeneration.Molecular neurobiology · 2022Review
- Melatonin alleviates traumatic brain injury-induced anxiety-like behaviors in rats: Roles of the protein kinase A/cAMP-response element binding signaling pathway.Experimental and therapeutic medicine · 2022Article
- Tau Acts in Concert With Kinase/Phosphatase Underlying Synaptic Dysfunction.Frontiers in aging neuroscience · 2022Review
- Illuminating Neural Circuits in Alzheimer's Disease.Neuroscience bulletin · 2021Review
- Medial septum tau accumulation induces spatial memory deficit via disrupting medial septum-hippocampus cholinergic pathway.Clinical and translational medicine · 2021Article
- Tau-induced upregulation of C/EBPβ-TRPC1-SOCE signaling aggravates tauopathies: A vicious cycle in Alzheimer neurodegeneration.Aging cell · 2020Article
- Phosphodiesterase Inhibitors for Alzheimer's Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale.Journal of Alzheimer's disease reports · 2020Review
- Tau inhibits PKA by nuclear proteasome-dependent PKAR2α elevation with suppressed CREB/GluA1 phosphorylation.Aging cell · 2020Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Intraneuronal accumulation of wild-type tau plays a key role in Alzheimer's disease, while the mechanisms underlying tauopathy and memory impairment remain unclear. Here, we report that overexpressing full-length wild-type human tau (hTau) in mouse hippocampus induces learning and memory deficits with remarkably reduced levels of multiple synapse- and memory-associated proteins. Overexpressing hTau inhibits the activity of protein kinase A (PKA) and decreases the phosphorylation level of cAMP-response element binding protein (CREB), GluA1, and TrkB with reduced BDNF mRNA and protein levels both in vitro and in vivo. Simultaneously, overexpressing hTau increased PKAR2α (an inhibitory subunit of PKA) in nuclear fraction and inactivated proteasome activity. With an increased association of PKAR2α with PA28γ (a nuclear proteasome activator), the formation of PA28γ-20S proteasome complex remarkably decreased in the nuclear fraction, followed by a reduced interaction of PKAR2α with 20S proteasome. Both downregulating PKAR2α by shRNA and upregulating proteasome by expressing PA28γ rescued hTau-induced PKA inhibition and CREB dephosphorylation, and upregulating PKA improved hTau-induced cognitive deficits in mice. Together, these data reveal that intracellular tau accumulation induces synapse and memory impairments by inhibiting PKA/CREB/BDNF/TrkB and PKA/GluA1 signaling, and deficit of PA28γ-20S proteasome complex formation contributes to PKAR2α elevation and PKA inhibition.
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