ArticleNeurobiology of disease2020
Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration.
Article in Neurobiology of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 133 citations in OpenAlex.
- Significance of NAD anabolism profiles in neurological diseases.Metabolic brain disease · 2026Review
- Peripheral Neuropathy in Metabolic Stress.International journal of molecular sciences · 2026Review
- Loss of SARM1 Improves Phenotypes in a Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.Neurology. Genetics · 2026Article
- Wallerian Degeneration and Nerve Regeneration-A Review of Cellular and Molecular Events.International journal of molecular sciences · 2026Review
- A human iPSC-derived sensory neuron platform for high-throughput discovery of neuroprotectants against chemotherapy-induced peripheral neuropathy.Cell reports. Medicine · 2026Article
- The rise and fall of SARM1 base-exchange inhibitors.Communications chemistry · 2026Article
- Programmed axon degeneration: mechanism, inhibition and therapeutic potential.Nature reviews. Neuroscience · 2026Review
- NAD⁺ Reduction in Glutamatergic Neurons Induces Lipid Catabolism and Neuroinflammation in the Brain via SARM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phase-Specific Evaluation of Sciatic Nerve Regeneration in Preclinical Studies: A Review of Functional Assessment, Emerging Therapies, and Translational Value.International journal of molecular sciences · 2025Review
- A redox-dependent switch governing sensory axon degeneration and regeneration.Scientific reports · 2025Article
- Targeting SARM1 as a novel neuroprotective therapy in neurotropic viral infections.Journal of neuroinflammation · 2025Article
- Chronically Low NMNAT2 Expression Causes Sub-lethal SARM1 Activation and Altered Response to Nicotinamide Riboside in Axons.Molecular neurobiology · 2025Article
- The role of RGC degeneration in the pathogenesis of glaucoma.International journal of biological sciences · 2025Review
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- SARM1 in the pathogenesis of immune-related disease.Toxicology research · 2024Review
- Review
- The Physiologic Basis of Molecular Therapeutics for Peripheral Nerve Injury: A Primer.Journal of hand surgery global online · 2024Review
- SARM1-Dependent Axon Degeneration: Nucleotide Signaling, Neurodegenerative Disorders, Toxicity, and Therapeutic Opportunities.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Peripheral blood mononuclear cell respiratory function is associated with progressive glaucomatous vision loss.Nature medicine · 2024Article
- Augustus Waller's foresight realized: SARM1 in peripheral neuropathies.Current opinion in neurobiology · 2024Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Wallerian degeneration of physically injured axons involves a well-defined molecular pathway linking loss of axonal survival factor NMNAT2 to activation of pro-degenerative protein SARM1. Manipulating the pathway through these proteins led to the identification of non-axotomy insults causing axon degeneration by a Wallerian-like mechanism, including several involving mitochondrial impairment. Mitochondrial dysfunction is heavily implicated in Parkinson's disease, Charcot-Marie-Tooth disease, hereditary spastic paraplegia and other axonal disorders. However, whether and how mitochondrial impairment activates Wallerian degeneration has remained unclear. Here, we show that disruption of mitochondrial membrane potential leads to axonal NMNAT2 depletion in mouse sympathetic neurons, increasing the substrate-to-product ratio (NMN/NAD) of this NAD-synthesising enzyme, a metabolic fingerprint of Wallerian degeneration. The mechanism appears to involve both impaired NMNAT2 synthesis and reduced axonal transport. Expression of WLD
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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.