Autophagy is a regulated lysosomal degradation process that involves autophagosome formation and transport. Although recent evidence indicates that basal levels of autophagy protect against neurodegeneration, the exact mechanism whereby this occurs is not known. By using conditional knockout mutant mice, we report that neuronal autophagy is particularly important for the maintenance of local ho...

Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll...

Narcolepsy is a lifelong illness characterized by persistent sleepiness, hypnagogic hallucinations, and episodes of motor paralysis called cataplexy. We have tested the hypothesis that a transient neurodegenerative process is linked to symptom onset. Using the amino-cupric silver stain on brain sections from canine narcoleptics, we found elevated levels of axonal degeneration in the amygdala, b...

A 1.3-year-old Great Dane dog had a chronic progressive neurologic disease clinically expressed as a distal symmetrical polyneuropathy characterized by weakness and bilateral atrophy of bulbar and distal appendicular musculature. Qualitative and quantitative studies showed neurogenic atrophy of muscles below the elbow and stifle. There was Wallerian-type degeneration, Schwann cell proliferation...

Caspases have recently emerged as key regulators of axonal pruning and degeneration and of long-term depression (LTD), a long-lasting form of synaptic plasticity. However, the mechanism underlying these functions remains unclear. In this context, XIAP has been shown to modulate these processes. The neuron-specific form of FAIM protein (FAIM-L) is a death receptor antagonist that stabilizes XIAP...

The complex morphology of axons presents a challenge in understanding axonal responses to injury and disease. By in vivo two-photon imaging of spinal dorsal column sensory axons, we systematically examined the effect of injury location relative to the main bifurcation point on axon degeneration and regeneration following highly localized laser injuries. Retrograde but not anterograde degenerati...