Neuronal death underlies the symptoms of many human neurological disorders, including Alzheimer's, Parkinson's and Huntington's diseases, stroke, and amyotrophic lateral sclerosis. The identification of specific genetic and environmental factors responsible for these diseases has bolstered evidence for a shared pathway of neuronal death — apoptosis — involving oxidative stress, perturbed calcium homeostasis, mitochondrial dysfunction and activation of cysteine proteases called caspases. These death cascades are counteracted by survival signals, which suppress oxyradicals and stabilize calcium homeostasis and mitochondrial function. With the identification of mechanisms that either promote or prevent neuronal apoptosis come new approaches for preventing and treating neurodegenerative disorders.

Neuronal death underlies the symptoms of many human neurological disorders, including Alzheimer's, Parkinson's and Huntington's diseases, stroke, and amyotrophic lateral sclerosis. Many signals can initiate apoptosis in neurons, including lack of neurotrophic factor support, overactivation of glutamate receptors (leading to calcium influx), increased oxidative stress and metabolic stress. Mitochondrial changes are pivotal in the cell death decision in many cases. Mitochondria in cells undergoing apoptosis show increased oxyradical production, opening of pores in their membranes and release of cytochrome c.The Bcl-2 family of proteins includes both anti-apoptotic (for example, Bcl-2) and pro-apoptotic (for example, Bax) members.Overexpression of Bcl-2 in cell cultures and in transgenic mice increases resistance of neurons to death induced by excitotoxic, metabolic and oxidative insults. Conversely, neurons lacking Bax are protected against apoptosis.Further mechanisms that can regulate the early stages of apoptosis in neurons involve caspases (evolutionarily conserved cysteine proteases central to apoptosis of many cell types), Par-4 and telomerase.