Prolonged axonal survival in transected nerves of C57BL/Ola mice is independent of age

Crawford, Thomas O.; Hsieh, Sung‐Tsang; Schryer, Brenda L.; Glass, Jonathan D.

doi:10.1007/bf01189060

Cited by 24 publications

(18 citation statements)

References 20 publications

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“…To put this low stringency in perspective, most axons in Wld S homozygotes survive structurally even 14 days after lesioning. 6,15,23,24 First, we studied 3-day lesioned distal nerve stumps using electron microscopy ( Figure 3 and Supplementary Figure 3). In Wld S heterozygotes, most axons displayed normal cytoskeleton, unswollen mitochondria and a regular myelin sheath of normal thickness.…”

Section: Resultsmentioning

confidence: 99%

NAD+ and axon degeneration revisited: Nmnat1 cannot substitute for WldS to delay Wallerian degeneration

et al. 2006

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The slow Wallerian degeneration protein (Wld S ), a fusion protein incorporating full-length nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), delays axon degeneration caused by injury, toxins and genetic mutation. Nmnat1 overexpression is reported to protect axons in vitro, but its effect in vivo and its potency remain unclear. We generated Nmnat1-overexpressing transgenic mice whose Nmnat activities closely match that of Wld S mice. Nmnat1 overexpression in five lines of transgenic mice failed to delay Wallerian degeneration in transected sciatic nerves in contrast to Wld S mice where nearly all axons were protected. Transected neurites in Nmnat1 transgenic dorsal root ganglion explant cultures also degenerated rapidly. The delay in vincristine-induced neurite degeneration following lentiviral overexpression of Nmnat1 was significantly less potent than for Wld S , and lentiviral overexpressed enzyme-dead Wld S still displayed residual neurite protection. Thus, Nmnat1 is significantly weaker than Wld S at protecting axons against traumatic or toxic injury in vitro, and has no detectable effect in vivo. The full protective effect of Wld S requires more N-terminal sequences of the protein.

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Section: Resultsmentioning

confidence: 99%

NAD+ and axon degeneration revisited: Nmnat1 cannot substitute for WldS to delay Wallerian degeneration

et al. 2006

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“…No protection was seen in the SOD1 G37R or SOD1 G85R mice [51] . This result could be explained by the observation that the Wld S protective phenotype only lasts 2-3 weeks after injury [52] , and is diminished after 3 months of age at the most terminal portions of the axon [53] . Therefore, Wld S may be more effective in acute processes or in early-onset disease, such as pmn, and protection may be lost in chronic disease models [48] .…”

Section: Axonal Degeneration Is Independent Of Cell Deathmentioning

confidence: 91%

Axonal Degeneration in Motor Neuron Disease

Fischer¹,

Glass

2007

Neurodegener Dis

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126

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Growing evidence from animal models and patients with amyotrophic lateral sclerosis (ALS) suggests that distal axonal degeneration begins very early in this disease, long before symptom onset and motor neuron death. The cause of axonal degeneration is unknown, and may involve local axonal damage, withdrawal of trophic support from a diseased cell body, or both. It is increasingly clear that axons are not passive extensions of their parent cell bodies, and may die by mechanisms independent of cell death. This is supported by studies in which protection of motor neurons in models of ALS did not significantly improve symptoms or prolong lifespan, likely due to a failure to protect axons. Here, we will review the evidence for early axonal degeneration in ALS, and discuss possible mechanisms by which it might occur, with a focus on oxidative stress. We contend that axonal degeneration may be a primary feature in the pathogenesis of motor neuron disease, and that preventing axonal degeneration represents an important therapeutic target that deserves increased attention.

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“…Although one study showed that the prolonged survival of axons in transected nerves of Wlds mice is independent of age, 91 most other studies found that the Wlds phenotype is age-dependent. One study showed that although the expression of Wlds protein was independent of age in these mice, loss of ability of the sciatic nerve to conduct action potentials after transection is much more rapid in mice one year of age when compared to one month old animals.…”

Section: Age Nad and Neural Protectionmentioning

confidence: 98%

NAD and axon degeneration: From the Wlds gene to neurochemistry

Wang¹,

He²

2009

Cell Adhesion & Migration

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Neurodegenerative diseases have become a global issue due to the aging population. These disorders affect a vast patient population and represent a huge area of unmet therapeutic need. Axon degeneration is a common pathological character of those neurodegenerative diseases. It results in the loss of communication between neurons. Two decades ago, the Wallerian degeneration slow (Wlds) mouse strain was identified, in which the degeneration of transected axons is delayed. The phenotype is attributed to the overexpression of a chimeric protein Wlds which contains a short fragment of the ubiquitin assembly protein UFD2 and the full-length nicotinamide adenine dinucleotide (NAD) synthetic enzyme Nicotinamide mononucleotide adenylyl-transferase-1 (Nmnat-1). However, the underlying molecular mechanism remains largely unknown. Recently, it's reported by independent researchers that the full length coding sequence of mouse Nmnat-1 could mimic the axonal protective effect of the Wlds gene when overexpressed in primary neural cultures. Together with a significant number of subsequential reports, this finding highlighted the substantial role of nicotinamide adenine dinucleotide (NAD) in the process of axon degeneration. Here we reviewed the history of axon degeneration research from a neurochemical standpoint and discuss the potential involvement of NAD synthesis, NAD consumption and NAD-dependent proteins and small molecules in axon degeneration.

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Prolonged axonal survival in transected nerves of C57BL/Ola mice is independent of age

Cited by 24 publications

References 20 publications

NAD+ and axon degeneration revisited: Nmnat1 cannot substitute for WldS to delay Wallerian degeneration

NAD+ and axon degeneration revisited: Nmnat1 cannot substitute for WldS to delay Wallerian degeneration

Axonal Degeneration in Motor Neuron Disease

NAD and axon degeneration: From the Wlds gene to neurochemistry

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