Mechanisms of neurotoxic injury and cell death

Neurotoxic injury to the nervous system usually produces neuronal death or distal axonal degeneration. Neurotoxin-induced demyelination is relatively rare in both the PNS and CNS. Major advances have occurred in our understanding of the mechanism of excitotoxic and apoptotic cell death. The pathways leading to apoptosis offer many new approaches to neuroprotection. The most promising is the use of specific neuronal growth factors (NGF, BDNF, NT3, IGF-I, etc.) to prevent neurotoxicity. All of these growth factors seem to be able to regulate the mitochondrial/cytochrome c pathway. The development of therapeutic strategies to prevent neurotoxic injury has broad implications. Many neurodegenerative and metabolic disorders of the nervous system probably involve similar death pathways. These mechanism-based approaches to preventing neurotoxic injury will generate potential therapies for other neurologic disorders. The chemotherapeutic neurotoxins are valuable models because prospective human trials are uniquely possible. Treatment can be administered before the neurotoxic insult is administered; usually under carefully controlled conditions.