ArticleNeuron2012
JNK3 perpetuates metabolic stress induced by Aβ peptides.
Article in Neuron, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
126 citing papers in PubMed, 3 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models.BMC neuroscience · 2025Pooled it
- Protective Effects of Nicotinamide Adenine Dinucleotide and Related Precursors in Alzheimer's Disease: A Systematic Review of Preclinical Studies.Journal of molecular neuroscience : MN · 2021Pooled it
- A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease.Frontiers in neuroscience · 2021Pooled it
- Article
- Study on Regulatory Mechanism ofMolecules (Basel, Switzerland) · 2026Article
- Review
- Protein kinases as therapeutic targets in Alzheimer's disease: challenges, insights, and new frontiers.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Low concentrations of amyloid-beta oligomers induce synaptogenesis characteristic for mild cognitive impairment and alter the de novo proteome.Translational psychiatry · 2026Article
- Targeting JNK3: AnCNS & neurological disorders drug targets · 2026Article
- Protein Kinases in Alzheimer's Disease: Pioneering Insights into Pathogenesis and Therapeutic Breakthroughs.Current neuropharmacology · 2026Review
- JNK3 quantification in plasma: a novel biomarker for neuronal damage in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Advances in JNK inhibitor development: therapeutic prospects in neurodegenerative diseases and fibrosis.Archives of pharmacal research · 2025Review
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- The UFMylation pathway is impaired in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Identification of potential JNK3 inhibitors through virtual screening, molecular docking and molecular dynamics simulation as therapeutics for Alzheimer's disease.Molecular diversity · 2024Article
- CaMKK2: bridging the gap between Ca2+ signaling and energy-sensing.Essays in biochemistry · 2024Review
- JNK inhibitor and ferroptosis modulator as possible therapeutic modalities in Alzheimer disease (AD).Scientific reports · 2024Article
- The role of AMPKα subunit in Alzheimer's disease: In-depth analysis and future prospects.Heliyon · 2024Review
- Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy.International journal of molecular sciences · 2024Review
- The UFMylation pathway is impaired in Alzheimer's disease.bioRxiv : the preprint server for biology · 2024Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Although Aβ peptides are causative agents in Alzheimer's disease (AD), the underlying mechanisms are still elusive. We report that Aβ42 induces a translational block by activating AMPK, thereby inhibiting the mTOR pathway. This translational block leads to widespread ER stress, which activates JNK3. JNK3 in turn phosphorylates APP at T668, thereby facilitating its endocytosis and subsequent processing. In support, pharmacologically blocking translation results in a significant increase in Aβ42 in a JNK3-dependent manner. Thus, JNK3 activation, which is increased in human AD cases and a familial AD (FAD) mouse model, is integral to perpetuating Aβ42 production. Concomitantly, deletion of JNK3 from FAD mice results in a dramatic reduction in Aβ42 levels and overall plaque loads and increased neuronal number and improved cognition. This reveals AD as a metabolic disease that is under tight control by JNK3.
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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.