Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DR...

Methamphetamine (meth) is a neurotoxic psychostimulant that increases monoamine oxidase (MAO)-dependent mitochondrial oxidant stress in axonal but not somatic compartments of substantia nigra pars compacta (SNc) and locus coeruleus (LC) neurons. Chronic meth administration results the degeneration SNc LC neurons male mice, MAO inhibition neuroprotective, suggesting deleterious effects chronic b...

Myelinating glia cells support axon survival and functions through mechanisms independent of myelination, and their dysfunction leads to axonal degeneration in several diseases. In amyotrophic lateral sclerosis (ALS), spinal motor neurons undergo retrograde degeneration, and slowing of axonal transport is an early event that in ALS mutant mice occurs well before motor neuron degeneration. Inter...

Axonal degeneration often leads to the death of neuronal cell bodies. Previous studies have demonstrated the crucial role of nicotinamide adenine dinucleotide (NAD) biosynthesis in axonal protection of motor neurons, but the role of nicotinamide mononucleotide adenylyltransferase 1 and NAD in optic nerve degeneration is unclear. Intravitreal injection of tumor necrosis factor (TNF) induces opti...

SARM1 is a key regulator of axonal degeneration. However, SARM1 mechanism of action is not clear. In this issue of Neuron, Essuman et al. (2017) reveal an intrinsic NADase activity in the SARM1-TIR domain that is required for axonal degeneration.

Myelination increases neuronal conduction velocity through its insulating properties and an unidentified extrinsic effect that increases axonal caliber. Although it is well established that demyelination can cause axonal atrophy, the myelin molecule that regulates axonal caliber is not known. Loss of the structural proteins of compact peripheral nervous system (PNS) myelin, P0 protein, and myel...

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...

Progressive axonal degeneration follows demyelination in many neurological diseases, including multiple sclerosis and inherited demyelinating neuropathies, such as Charcot-Marie-Tooth disease. One glial molecule, the myelin-associated glycoprotein (MAG), located in the adaxonal plasmalemma of myelin-producing cells, is known to signal to the axon and to modulate axonal caliber through phosphory...

Axonal degeneration is the major cause of permanent neurological disability in individuals with inherited diseases of myelin. Axonal and neuronal changes that precede axonal degeneration, however, are not well characterized. We show here that dysmyelinated lower motor neurons retract and regenerate dysfunctional presynaptic terminals, leading to severe neurological disability before axonal dege...

Abnormalities and impairments in axonal transport are suggested to strongly contribute to the pathological alterations underlying AD. The exact mechanisms leading to axonopathy are currently unclear, but it was recently suggested that APP expression itself triggers axonal degeneration. We used APP transgenic mice and crossed them on a hemi- or homozygous PS1 knock-in background (APP/PS1KI). Dep...