ArticleCell death & disease2017
Induction of autophagy by spermidine is neuroprotective via inhibition of caspase 3-mediated Beclin 1 cleavage.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Pooled it
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- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Article
- Age-Specific Ex Vivo Modulation of Gut-Brain Axis-Associated Metabolites by Galacto-Oligosaccharides and Nutrient Blends in Early Childhood.Metabolites · 2026Article
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Mitophagy-NLRP3 Inflammasome Crosstalk in Parkinson's Disease: Pathogenic Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Spermidine in Alzheimer's Disease: Evidence from Animal Models and Human Studies.Degenerative neurological and neuromuscular disease · 2026Review
- The Role of Immunosenescence and Inflammaging in the Susceptibility of Older Adults to SARS-CoV-2 Infection.Current pharmaceutical biotechnology · 2026Review
- Exploring Autophagy Inducing Molecules: Targeting Diverse Pathways in Alzheimer's Disease Management.Medicinal research reviews · 2026Review
- Opposite effects of spermidine and GC7 in cell culture are dictated by distinct molecular targets.The Biochemical journal · 2025Article
- Prolonged Survival with Dieting for Improved Autophagy.Non-coding RNA · 2025Review
- Review
- A brain microbiome in salmonids at homeostasis.Science advances · 2024Article
- Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF.Aesthetic plastic surgery · 2024Article
- Reduction of spermine synthase enhances autophagy to suppress Tau accumulation.Cell death & disease · 2024Article
- Advanced age and female sex protect cerebral arteries from mitochondrial depolarization and apoptosis during acute oxidative stress.Aging cell · 2024Article
- Possible Role of Cellular Polyamine Metabolism in Neuronal Apoptosis.Current medical science · 2024Article
- Molecular mechanism of caloric restriction mimetics-mediated neuroprotection of age-related neurodegenerative diseases: an emerging therapeutic approach.Biogerontology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spermidine, a natural polyamine presented widely in mammalian cells, has been implicated to extend the lifespan of several model organisms by inducing autophagy. However, the effect of spermidine against neuronal damage has not yet been fully determined. In this study, neuronal cell injury was induced by treating PC12 cells and cortical neurons with 1 μM staurosporine (STS). We found that STS-induced cell injury could be efficiently attenuated by pretreatment with 1 mM spermidine. Spermidine inhibited the caspase 3 activation induced by STS. Moreover, STS incubation resulted in autophagic degradation failure, which could be attenuated by the pretreatment of spermidine. Knocking down the expression of Beclin 1 efficiently suppressed autophagosome and autolysosome accumulation, and abolished the protective effects of spermidine against STS-induced neurotoxicity. Increased Beclin 1 cleavage and partial nuclear translocation of Beclin 1 fragment was detected in STS-treated cells, which could be blocked by spermidine, pan-caspase inhibitor or caspase 3-specific inhibitor. The nuclear translocation of Beclin 1 fragment universally occurs in damaged neurons. Beclin 1 mutation at the sites of 146 and 149 prevented the intracellular re-distribution of Beclin 1 induced by STS. In addition, intraperitoneal injection of spermidine ameliorated ischemia/reperfusion-induced neuronal injury in the hippocampus and cortex of rats, possibly via blocking caspase 3 activation and consequent Beclin 1 cleavage. Our findings suggest that caspase 3-mediated Beclin 1 cleavage occurs in acute neuronal cell injury both in vitro and in vivo. The neuroprotective effect of spermidine may be related to inhibition of the caspase 3-mediated Beclin 1 cleavage and restoration of the Beclin 1-dependent autophagy.
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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.