ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Involvement of caspase-6 and caspase-8 in neuronal apoptosis and the regenerative failure of injured retinal ganglion cells.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 102 citations in OpenAlex.
- Advances inMicroorganisms · 2025Review
- Caspase-mediated pathways in retinal ganglion cell injury: a novel therapeutic target for glaucoma.Frontiers in cell and developmental biology · 2025Review
- Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration.International journal of molecular sciences · 2024Review
- Apoptosis in glaucoma: A new direction for the treatment of glaucoma (Review).Molecular medicine reports · 2024Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Inhibition of ferroptosis promotes retina ganglion cell survival in experimental optic neuropathies.Redox biology · 2022Article
- Hematogenous Macrophages Contribute to Fibrotic Scar Formation After Optic Nerve Crush.Molecular neurobiology · 2022Article
- The proteome of distal nerves: implication in delayed repair and poor functional recovery.Neural regeneration research · 2022Article
- Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells' response to Pten deletion.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals.Clinical epigenetics · 2021Article
- Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer's Disease.Acta neuropathologica communications · 2021Article
- RNA-Seq reveals differential expression profiles and functional annotation of genes involved in retinal degeneration in Pde6c mutant Danio rerio.BMC genomics · 2020Article
- Involvement of the miR-137-3p/CAPN-2 Interaction in Ischemia-Reperfusion-Induced Neuronal Apoptosis through Modulation of p35 Cleavage and Subsequent Caspase-8 Overactivation.Oxidative medicine and cellular longevity · 2020Article
- Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils.Pharmaceutical biology · 2019Article
- Prospective Application of Activity-Based Proteomic Profiling in Vision Research-Potential Unique Insights into Ocular Protease Biology and Pathology.International journal of molecular sciences · 2019Review
- Modifying PTEN recruitment promotes neuron survival, regeneration, and functional recovery after CNS injury.Cell death & disease · 2019Article
- Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Cognitive Deficits Following a Post-Myocardial Infarct in the Rat Are Blocked by the Serotonin-Norepinephrine Reuptake Inhibitor Desvenlafaxine.International journal of molecular sciences · 2018Article
- Physiological functions of non-apoptotic caspase activity in the nervous system.Seminars in cell & developmental biology · 2018Review
- Caspase vinyl sulfone small molecule inhibitors prevent axonal degeneration in human neurons and reverse cognitive impairment in Caspase-6-overexpressing mice.Molecular neurodegeneration · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
To promote functional recovery after CNS injuries, it is crucial to develop strategies that enhance both neuronal survival and regeneration. Here, we report that caspase-6 is upregulated in injured retinal ganglion cells and that its inhibition promotes both survival and regeneration in these adult CNS neurons. Treatment of rat retinal whole mounts with Z-VEID-FMK, a selective inhibitor of caspase-6, enhanced ganglion cell survival. Moreover, retinal explants treated with this drug extended neurites on myelin. We also show that caspase-6 inhibition resulted in improved ganglion cell survival and robust axonal regeneration following optic nerve injury in adult rats. The effects of Z-VEID-FMK were similar to other caspase inhibitory peptides including Z-LEHD-FMK and Z-VAD-FMK. In searching for downstream effectors for caspase-6, we identified caspase-8, whose expression pattern resembled that of caspase-6 in the injured eye. We then showed that caspase-8 is activated downstream of caspase-6 in the injured adult retina. Furthermore, we investigated the role of caspase-8 in RGC apoptosis and regenerative failure both in vitro and in vivo. We observed that caspase-8 inhibition by Z-IETD-FMK promoted survival and regeneration to an extent similar to that obtained with caspase-6 inhibition. Our results indicate that caspase-6 and caspase-8 are components of a cellular pathway that prevents neuronal survival and regeneration in the adult mammalian CNS.
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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.