ArticlePLoS genetics2012
Diapause formation and downregulation of insulin-like signaling via DAF-16/FOXO delays axonal degeneration and neuronal loss.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 70 citations in OpenAlex.
- A Phase 1 randomized study on the safety and pharmacokinetics of OCS-05, a neuroprotective disease modifying treatment for Acute Optic Neuritis and Multiple Sclerosis.Scientific reports · 2023Trial
- The teneurin TEN-1 and its ligand LRON-11 support microbiota-induced neuroprotection and mechanosensory function in C. elegans.Current biology : CB · 2026Article
- Article
- ILP4 and InR regulate paclitaxel-induced hypersensitivity differently inMolecular biology of the cell · 2026Article
- Insulin-like Growth Factor 1 Impact on Alzheimer's Disease: Role in Inflammation, Stress, and Cognition.Current issues in molecular biology · 2025Review
- Independent control of functional rewiring after axon injury byJournal of biosciences · 2025Article
- Article
- The diverse functions of the DEG/ENaC family: linking genetic and physiological insights.The Journal of physiology · 2023Article
- Article
- Pathophysiology of neurodegenerative diseases: An interplay among axonal transport failure, oxidative stress, and inflammation?Seminars in immunology · 2022Review
- Regulation of UNC-40/DCC and UNC-6/Netrin by DAF-16 promotes functional rewiring of the injured axon.Development (Cambridge, England) · 2021Article
- Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification.Nature communications · 2021Article
- Neuronal lipolysis participates in PUFA-mediated neural function and neurodegeneration.EMBO reports · 2020Article
- Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair.JMIR research protocols · 2020Article
- Effects of NADBiomolecules · 2020Review
- Article
- Axonal Degeneration in AD: The Contribution of Aβ and Tau.Frontiers in aging neuroscience · 2020Review
- Comparative Transcriptomic Analysis Reveals Molecular Profiles of Central Nervous System in Maternal Diapause Induction ofG3 (Bethesda, Md.) · 2019Article
- Altered mitochondrial bioenergetics are responsible for the delay in Wallerian degeneration observed in neonatal mice.Neurobiology of disease · 2019Article
- Axonal Degeneration Is Mediated by Necroptosis Activation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Axonal degeneration is a key event in the pathogenesis of neurodegenerative conditions. We show here that mec-4d triggered axonal degeneration of Caenorhabditis elegans neurons and mammalian axons share mechanistical similarities, as both are rescued by inhibition of calcium increase, mitochondrial dysfunction, and NMNAT overexpression. We then explore whether reactive oxygen species (ROS) participate in axonal degeneration and neuronal demise. C. elegans dauers have enhanced anti-ROS systems, and dauer mec-4d worms are completely protected from axonal degeneration and neuronal loss. Mechanistically, downregulation of the Insulin/IGF-1-like signaling (IIS) pathway protects neurons from degenerating in a DAF-16/FOXO-dependent manner and is related to superoxide dismutase and catalase-increased expression. Caloric restriction and systemic antioxidant treatment, which decrease oxidative damage, protect C. elegans axons from mec-4d-mediated degeneration and delay Wallerian degeneration in mice. In summary, we show that the IIS pathway is essential in maintaining neuronal homeostasis under pro-degenerative stimuli and identify ROS as a key intermediate of neuronal degeneration in vivo. Since axonal degeneration represents an early pathological event in neurodegeneration, our work identifies potential targets for therapeutic intervention in several conditions characterized by axonal loss and functional impairment.
Indexed as
Identifiers
What OpenQuestion holds
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.