ArticleAlzheimer's research & therapy2025
Hampered AMPK-ULK1 cascade in Alzheimer's disease (AD) instigates mitochondria dysfunctions and AD-related alterations which are alleviated by metformin.
Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Energy stress activates AMPK to suppress ferroptosis in neurodegenerative proteinopathies.International journal of molecular medicine · 2026Article
- Discovery and preclinical validation of a translationally optimized mitochondrial complex I modulator for Alzheimer's disease.npj drug discovery · 2026Article
- Fisetin Attenuates Amyloid-Beta-Induced Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells: Integrating In Silico Target Prediction and In Vitro Validation.Journal of biochemical and molecular toxicology · 2026Article
- Brain insulin resistance as a driver of proteinopathy in neurodegeneration: from cell-type-specific mechanisms to targeted therapeutics.Translational neurodegeneration · 2026Review
- Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology.Nature aging · 2026Article
- Review
- The therapeutic potential of botanicals: how medicinal plants targeting autophagy can reverse metabolic-associated fatty liver disease.Frontiers in pharmacology · 2026Review
- Molecular mechanisms underlying exercise-enhanced autophagy in improving neuroplasticity in Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- Calibrating microglia states in Alzheimer's disease: decoding immune-metabolic networks and nano-targeted multicomponent therapies.Frontiers in immunology · 2026Review
- Multiple Mechanisms and Therapeutic Strategies for the Involvement of AMPK in the Development of Alzheimer's Disease.Molecular neurobiology · 2025Review
- Advances in the Understanding of Mitochondrial Inflammatory Regulation in the Pathogenesis of Alzheimer's Disease.Journal of inflammation research · 2025Review
- Article
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Authors and funding
11 authors.
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Abstract
The adenosine monophosphate-activated protein kinase (AMPK) and its downstream effector Unc-51 like autophagy activating kinase 1 (ULK1) represent a key cellular signaling node, the alteration of which likely contribute to AD development. This study investigated the AMPK-ULK1 pathway activation state in AD and the impact of its modulation on mitochondria structure and function as well as on AD-related alterations. We show in human sporadic AD and 3xTgAD mice brains a defective activating phosphorylation of ULK1 despite the active phosphorylation of AMPK. In addition, we reported defective p-AMPK and p-ULK1 in cells expressing the amyloid precursor protein with the familial Swedish mutation. We then show that the antidiabetic metformin (Met) drug-mediated AMPK-ULK1 cascade activation alleviates structural and functional mitochondrial abnormalities in AD cells and mice brains. Furthermore, in the 3xTgAD brains, it reduces the early accumulation of APP C-terminal fragments (APP-CTFs) as well as amyloid beta (Aβ) burden, microgliosis and astrogliosis occurring at a later disease stage. AMPK-ULK1 activation increases the localization of APP-CTFs within cathepsin D-positive lysosomal compartments and the recruitment of Iba1
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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 Socratic graph.