ArticleMolecular neurodegeneration2012
WldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity.
Article in Molecular neurodegeneration, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Nicotinamide Mononucleotide Adenylyltransferase 1 and NADMetabolites · 2026Review
- Programmed axon degeneration: mechanism, inhibition and therapeutic potential.Nature reviews. Neuroscience · 2026Review
- White matter lesions contribute to motor and non-motor disorders in Parkinson's disease: a critical review.GeroScience · 2025Review
- Tau-mediated axonal degeneration is prevented by activation of the WldBrain communications · 2023Article
- Genetic diversity of axon degenerative mechanisms in models of Parkinson's disease.Neurobiology of disease · 2021Article
- Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration.Neurobiology of disease · 2020Article
- The challenge of regenerative therapies for the optic nerve in glaucoma.Experimental eye research · 2017Review
- Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.Scientific reports · 2017Article
- Nicotinamide and WLDFrontiers in neuroscience · 2017Article
- The axon-protective WLD(S) protein partially rescues mitochondrial respiration and glycolysis after axonal injury.Journal of molecular neuroscience : MN · 2015Article
- Upregulation of cell surface estrogen receptor alpha is associated with the mitogen-activated protein kinase/extracellular signal-regulated kinase activity and promotes autophagy maturation.International journal of clinical and experimental pathology · 2015Article
- Wallerian degeneration: an emerging axon death pathway linking injury and disease.Nature reviews. Neuroscience · 2014Review
- The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons.Molecular neurodegeneration · 2014Article
- Axon degeneration and PGC-1α-mediated protection in a zebrafish model of α-synuclein toxicity.Disease models & mechanisms · 2014Article
- NMNATs, evolutionarily conserved neuronal maintenance factors.Trends in neurosciences · 2013Review
- MPP+-induces PUMA- and p53-dependent, but ATF3-independent cell death.Toxicology letters · 2013Article
- Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain.PloS one · 2013Article
- Retinal ganglion cell survival and axon regeneration in WldS transgenic rats after optic nerve crush and lens injury.BMC neuroscience · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe WldS mouse mutant ("Wallerian degeneration-slow") delays axonal degeneration in a variety of disorders including in vivo models of Parkinson's disease. The mechanisms underlying WldS -mediated axonal protection are unclear, although many studies have attributed WldS neuroprotection to the NAD+-synthesizing Nmnat1 portion of the fusion protein. Here, we used dissociated dopaminergic cultures to test the hypothesis that catalytically active Nmnat1 protects dopaminergic neurons from toxin-mediated axonal injury.
resultsUsing mutant mice and lentiviral transduction of dopaminergic neurons, the present findings demonstrate that WldS but not Nmnat1, Nmnat3, or cytoplasmically-targeted Nmnat1 protects dopamine axons from the parkinsonian mimetic N-methyl-4-phenylpyridinium (MPP+). Moreover, NAD+ synthesis is not required since enzymatically-inactive WldS still protects. In addition, NAD+ by itself is axonally protective and together with WldS is additive in the MPP+ model.
conclusionsOur data suggest that NAD+ and WldS act through separate and possibly parallel mechanisms to protect dopamine axons. As MPP+ is thought to impair mitochondrial function, these results suggest that WldS might be involved in preserving mitochondrial health or maintaining cellular metabolism.
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