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) part...

Axonal degeneration is a key pathological feature of several neurological disorders. Emerging evidence has suggested a pathological connection between axonal degeneration and autophagy, a lysosomal degradation pathway. We recently reported that GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote axonal degeneration. GSK3B-MCL1 pathway affects ATP production locally in d...

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that inflammation, demyelination, oligodendrocyte loss, gliosis, axonal injury and neurodegeneration are the main histopathological hallmarks of the disease. Although MS was classically thought as a demyelinating disease, but axonal injury occurs commonly in acute inflammatory lesions. In MS mi...

In chronic neurodegenerative syndromes, neurons progressively die through a generalized retraction pattern triggering retrograde axonal degeneration toward the cell bodies, which molecular mechanisms remain elusive. Recent observations suggest that direct activation of pro-apoptotic signaling in axons triggers local degenerative events associated with early alteration of axonal mitochondrial dy...

Axonal degeneration is a prominent feature of many forms of neurodegeneration, and also an early event in blast-mediated traumatic brain injury (TBI), the signature injury of soldiers in Iraq and Afghanistan. It is not known, however, whether this axonal degeneration is what drives development of subsequent neurologic deficits after the injury. The Wallerian degeneration slow strain (WldS) of m...

Axonal degeneration is a common pathological change of neurogenical disease which often arises before the neuron death. But it had not found any effective method to protect axon from degeneration. In this study we intended to confirm the protective effect of nicotinamide adenine dinucleotide (NAD), investigate the optimal administration dosage and time of NAD, and identify the relationship betw...

Peripheral neuropathies and Wallerian degeneration share a number of pathological features; the most prominent of which is axonal degeneration. We asked whether common pathophysiologic mechanisms are involved in these 2 disorders by directly comparing in vitro models of axonal degeneration after axotomy or exposure to the neurotoxin vincristine. Embryonic rat dorsal root ganglia (DRG) were allo...

Axonal degeneration is an early and important component of many neurological disorders. Overexpression of nicotinamide mononucleotide adenylyltransferase (Nmnat), a component of the slow Wallerian degeneration (Wld(s)) protein, protects axons from a variety of insults. We found that transduction of Nmnat protein into severed axons via virus-like particles prevented axonal degeneration. The post...

Axonal degeneration represents an early pathological event in neurodegeneration, constituting an important target for neuroprotection. Regardless of the initial injury, which could be toxic, mechanical, metabolic, or genetic, degeneration of axons shares a common mechanism involving mitochondrial dysfunction and production of reactive oxygen species. Critical steps in this degenerative process ...

Axonal degeneration is a major determinant of permanent neurological impairment during multiple sclerosis (MS). Due to the variable course of clinical disease and the heterogeneity of MS lesions, the mechanisms governing axonal degeneration may differ between disease stages. While the etiology of MS remains elusive, there now exist potential prognostic biomarkers that can predict the conversion...