Neuronal death occurs in many diseases of the peripheral nervous system including genetic, developmental, metabolic, degenerative, and toxic disorders. Specific diseases are mediated by one or several interlinked death-initiating pathways. These may involve oxidative stress, excitotoxicity, membrane disruption, loss of calcium homeostasis, DNA damage, trophic factor loss, or aberrant entry into the cell cycle. The death initiators activate two major final common pathways that lead to cell death. Necrosis is a catastrophic loss of ionic integrity caused by membrane disruption or loss of energy supply. Apoptosis is an endogenous programmed cell death pathway normally active in development and tissue homeostasis. It leads to orderly disassembly of the cell. Advances in understanding of the pathways from specific disease to neuronal death are leading to new strategies designed to prevent death and treat diseases of the nervous system.
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