ArticleThe Journal of clinical investigation2020
Brain-specific repression of AMPKα1 alleviates pathophysiology in Alzheimer's model mice.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 93 citations in OpenAlex.
- Discovery and preclinical validation of a translationally optimized mitochondrial complex I modulator for Alzheimer's disease.npj drug discovery · 2026Article
- Integrative physiology of skeletal muscle for maintaining cognitive health.The Journal of physiology · 2026Review
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- Prefrontal cortex-to-hypothalamic outputs orchestrate cue-potentiated palatable food consumption via AMPKβ2 signaling.Cell discovery · 2026Article
- Metabolic cell death networks in Alzheimer's disease: mechanistic links and therapeutic perspectives of ferroptosis, cuproptosis, and disulfidptosis.Frontiers in cell and developmental biology · 2026Review
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Molecular crosstalk for longevity: exercise and the AMPK/SIRT1/PGC-1α/Irisin/BDNF axis.Molecular biology reports · 2025Review
- AMPK/SIRT1/PGC-1α Signaling Pathway: Molecular Mechanisms and Targeted Strategies From Energy Homeostasis Regulation to Disease Therapy.CNS neuroscience & therapeutics · 2025Review
- Activation of the AMPK Signaling and Brain Function: A Friend or Foe?Journal of neurochemistry · 2025Review
- RNF168 dephosphorylation ameliorates cognitive decline in Aβ-based mouse models of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Activating AMPK improves pathological phenotypes due to mtDNA depletion.The FEBS journal · 2025Article
- Protection of Alzheimer's disease progression by a human-origin probiotics cocktail.Scientific reports · 2025Article
- Elongation factor 2 in cancer: a promising therapeutic target in protein translation.Cellular & molecular biology letters · 2024Review
- SIK1 Downregulates Synaptic AMPA Receptors and Contributes to Cognitive Defects in Alzheimer's Disease.Molecular neurobiology · 2024Article
- Suppression of neuronal AMPKβ2 isoform impairs recognition memory and synaptic plasticity.Neurobiology of disease · 2024Article
- Isoform-specific effects of neuronal inhibition of AMPK catalytic subunit on LTD impairments in a mouse model of Alzheimer's disease.Neurobiology of aging · 2024Article
- The role of AMPKα subunit in Alzheimer's disease: In-depth analysis and future prospects.Heliyon · 2024Review
- Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK.Cell metabolism · 2024Article
- Rejuvenating aged microglia by p16Molecular neurodegeneration · 2024Article
- Phosphoproteome Microarray Analysis of Extracellular Particles as a Tool to Explore Novel Biomarker Candidates for Alzheimer's Disease.International journal of molecular sciences · 2024Article
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10 authors at 3 institutions in 1 country.
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Abstract
AMPK is a key regulator at the molecular level for maintaining energy metabolism homeostasis. Mammalian AMPK is a heterotrimeric complex, and its catalytic α subunit exists in 2 isoforms: AMPKα1 and AMPKα2. Recent studies suggest a role of AMPKα overactivation in Alzheimer's disease-associated (AD-associated) synaptic failure. However, whether AD-associated dementia can be improved by targeting AMPK remains unclear, and roles of AMPKα isoforms in AD pathophysiology are not understood. Here, we showed distinct disruption of hippocampal AMPKα isoform expression patterns in postmortem human AD patients and AD model mice. We further investigated the effects of brain- and isoform-specific AMPKα repression on AD pathophysiology. We found that repression of AMPKα1 alleviated cognitive deficits and synaptic failure displayed in 2 separate lines of AD model mice. In contrast, AMPKα2 suppression did not alter AD pathophysiology. Using unbiased mass spectrometry-based proteomics analysis, we identified distinct patterns of protein expression associated with specific AMPKα isoform suppression in AD model mice. Further, AD-associated hyperphosphorylation of eukaryotic elongation factor 2 (eEF2) was blunted with selective AMPKα1 inhibition. Our findings reveal isoform-specific roles of AMPKα in AD pathophysiology, thus providing insights into potential therapeutic strategies for AD and related dementia syndromes.
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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.