ArticleThe Journal of biological chemistry2014
Rapamycin and interleukin-1β impair brain-derived neurotrophic factor-dependent neuron survival by modulating autophagy.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
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- Brain-Derived Neurotrophic Factor Deficiency Exacerbates Innate Immune Responses by Enhancing NLRP3 Inflammasome Activation and GSDMD-Mediated Pyroptosis in Mice.Medicina (Kaunas, Lithuania) · 2026Article
- Exploring Dapagliflozin's Influence on Autophagic Flux in Mania-like Behaviour: Insights from the LKB1/AMPK/LC3 Pathway in a Mouse Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Interlinked destinies: How ubiquitin-proteasome and autophagy systems underpin neurocognitive outcomes.Experimental neurology · 2024Review
- Agomelatine improves memory and learning impairments in a rat model of LPS-induced neurotoxicity by modulating the ERK/SorLA/BDNF/TrkB pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Molecular mechanisms and therapeutic potential of lithium in Alzheimer's disease: repurposing an old class of drugs.Frontiers in pharmacology · 2024Review
- The interplay between BDNF and PGC-1 alpha in maintaining brain health: role of exercise.Frontiers in endocrinology · 2024Review
- Mfap4: a promising target for enhanced liver regeneration and chronic liver disease treatment.NPJ Regenerative medicine · 2023Article
- Crosstalk Between Autophagy and Inflammation in Chronic Cerebral Ischaemia.Cellular and molecular neurobiology · 2023Review
- The Intersection of Innate Immune Pathways with the Latent Herpes Simplex Virus Genome.Journal of virology · 2023Review
- Swimming and L-arginine loaded chitosan nanoparticles ameliorates aging-induced neuron atrophy, autophagy marker LC3, GABA and BDNF-TrkB pathway in the spinal cord of rats.Pflugers Archiv : European journal of physiology · 2023Article
- Intranasal Administration of Resolvin E1 Produces Antidepressant-Like Effects via BDNF/VEGF-mTORC1 Signaling in the Medial Prefrontal Cortex.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Dimethyl fumarate abrogates striatal endoplasmic reticulum stress in experimentally induced late-stage Huntington's disease: Focus on the IRE1α/JNK and PERK/CHOP trajectories.Frontiers in pharmacology · 2023Article
- Neuroinflammation and Autophagy in Parkinson's Disease-Novel Perspectives.International journal of molecular sciences · 2022Review
- Using dual polarities of transcranial direct current stimulation in global cerebral ischemia and its following reperfusion period attenuates neuronal injury.Metabolic brain disease · 2022Article
- Quantitative proteomic analysis reveals the effects of mu opioid agonists on HT22 cells.Frontiers in pharmacology · 2022Article
- BDNF controls GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Neuronal Autophagy: Characteristic Features and Roles in Neuronal Pathophysiology.Biomolecules & therapeutics · 2021Review
- Downregulation of phosphoglycerate mutase 5 improves microglial inflammasome activation after traumatic brain injury.Cell death discovery · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The mammalian target of rapamycin (mTOR) pathway has multiple important physiological functions, including regulation of protein synthesis, cell growth, autophagy, and synaptic plasticity. Activation of mTOR is necessary for the many beneficial effects of brain-derived neurotrophic factor (BDNF), including dendritic translation and memory formation in the hippocampus. At present, however, the role of mTOR in BDNF's support of survival is not clear. We report that mTOR activation is necessary for BDNF-dependent survival of primary rat hippocampal neurons, as either mTOR inhibition by rapamycin or genetic manipulation of the downstream molecule p70S6K specifically blocked BDNF rescue. Surprisingly, however, BDNF did not promote neuron survival by up-regulating mTOR-dependent protein synthesis or through mTOR-dependent suppression of caspase-3 activation. Instead, activated mTOR was responsible for BDNF's suppression of autophagic flux. shRNA against the autophagic machinery Atg7 or Atg5 prolonged the survival of neurons co-treated with BDNF and rapamycin, suggesting that suppression of mTOR in BDNF-treated cells resulted in excessive autophagy. Finally, acting as a physiological analog of rapamycin, IL-1β impaired BDNF signaling by way of inhibiting mTOR activation as follows: the cytokine induced caspase-independent neuronal death and accelerated autophagic flux in BDNF-treated cells. These findings reveal a novel mechanism of BDNF neuroprotection; BDNF not only prevents apoptosis through inhibiting caspase activation but also promotes neuron survival through modulation of autophagy. This protection mechanism is vulnerable under chronic inflammation, which deregulates autophagy through impairing mTOR signaling. These results may be relevant to age-related changes observed in neurodegenerative diseases.
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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.