The gene for slow wallerian degeneration (Wld(s)) is also protective against vincristine neuropathy

Neurological diseases are frequently associated with axonal degeneration, w hich leads to dysfunction though separation of neurons from their targets. The mechanisms of axonal degeneration are largely unknown and in many cases are independent of those occurring within cell bodies in neurodegenerative disorders. The Wld(s) mouse mutant demonstrates the unique phenotype of re sistance to axonal degeneration after axotomy (slow Wallerian degeneration) , making it a powerful tool for studying mechanisms of axonal degeneration. We asked whether the Wld(s) mutation also provides resistance to axonal de generation in a slowly progressing neuropathy. Using cultured dorsal root g anglion neurons we compared the course of axonal degeneration in response t o exposure to the neurotoxin vincristine and found that Wld(s) neurites wer e relatively resistant to vincristine neuropathy. These findings suggest co mmon pathophysiologic mechanisms between axotomy-induced Wallerian degenera tion and toxic neuropathy. The implications are wide-ranging and are releva nt to the pathophysiology of axonal degeneration seen in a wide spectrum of neurological diseases ranging from stroke and head trauma to spinal cord i njury and peripheral neuropathy. (C) 2001 Academic Press.