ArticleCell death and differentiation2017
Global ischemia induces lysosomal-mediated degradation of mTOR and activation of autophagy in hippocampal neurons destined to die.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 113 citations in OpenAlex.
- Article
- Autophagy in ischemic stroke: from cellular survival mechanism to pathological damage.Metabolic brain disease · 2026Review
- ULK1 mediated autophagy in airway cells duringFrontiers in microbiology · 2026Article
- Autophagy and Neuropsychiatric Disorders: Unraveling Molecular Mechanisms and Signaling Pathways.CNS & neurological disorders drug targets · 2026Review
- MSC-Exosomes alleviate cognitive impairment after mild traumatic brain injury by inhibiting ferroptosis via PI3K/AKT/mTOR-mediated upregulation of GPX4.Functional & integrative genomics · 2025Article
- Lysosomal and mTORC1 signaling dysregulation underpin the pathology of spastic paraplegia type 80.Nature communications · 2025Article
- Tiny Messengers, Huge Consequences: Extracellular Vesicles and mTOR Signaling in Neuroinflammation.Journal of neurochemistry · 2025Review
- Microglial Autophagy and Mitophagy in Ischemic Stroke: From Dual Roles to Therapeutic Modulation.Biology · 2025Review
- Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion.Communications biology · 2025Article
- Synergistic Autophagy-Related Mechanisms of Protection Against Brain Aging and AD: Cellular Pathways and Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Transient Receptor Potential Vanilloid 4 Antagonist Eliminated Age-Related Spatial Memory Deficit in Female Sprague Dawley Rats.Neural plasticity · 2025Article
- Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS-induced colitis in a murine model.Journal of extracellular vesicles · 2024Article
- Deciphering the molecular mechanism of NLRP3 in BPA-mediated toxicity: Implications for targeted therapies.Heliyon · 2024Review
- Neuroprotective mechanisms of luteolin in glutamate-induced oxidative stress and autophagy-mediated neuronal cell death.Scientific reports · 2024Article
- Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones.Biomolecules · 2024Review
- Protein Kinase D Plays a Crucial Role in Maintaining Cardiac Homeostasis by Regulating Post-Translational Modifications of Myofilament Proteins.International journal of molecular sciences · 2024Article
- A crosstalk between autophagy and apoptosis in intracerebral hemorrhage.Frontiers in cellular neuroscience · 2024Review
- Protocol for establishing a global ischemia model using a 4-vessel occlusion in rats.STAR protocols · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The mammalian target of rapamycin (mTOR) is a key regulator of cell growth, autophagy, translation, and survival. Dysregulation of mTOR signaling is associated with cancer, diabetes, and autism. However, a role for mTOR signaling in neuronal death is not well delineated. Here we show that global ischemia triggers a transient increase in mTOR phosphorylation at S2448, whereas decreasing p-mTOR and functional activity in selectively vulnerable hippocampal CA1 neurons. The decrease in mTOR coincides with an increase in biochemical markers of autophagy, pS317-ULK-1, pS14-Beclin-1, and LC3-II, a decrease in the cargo adaptor p62, and an increase in autophagic flux, a functional readout of autophagy. This is significant in that autophagy, a catabolic process downstream of mTORC1, promotes the formation of autophagosomes that capture and target cytoplasmic components to lysosomes. Inhibitors of the lysosomal (but not proteasomal) pathway rescued the ischemia-induced decrease in mTOR, consistent with degradation of mTOR via the autophagy/lysosomal pathway. Administration of the mTORC1 inhibitor rapamycin or acute knockdown of mTOR promotes autophagy and attenuates ischemia-induced neuronal death, indicating an inverse causal relation between mTOR, autophagy, and neuronal death. Our findings identify a novel and previously unappreciated mechanism by which mTOR self-regulates its own levels in hippocampal neurons in a clinically relevant model of ischemic stroke.
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