Apoptotic neuronal death in Parkinson's disease: Involvement of nitric oxide

Apoptosis of nigral dopaminergic neurons by various mechanisms is an emerging phenomenon involved in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Both extrinsic and intrinsic pathways seems to be involved in death of nigral neurons, intrinsic pathway however, seems to be more important due to the energy crisis. Apoptosis by intrinsic pathway is executed by several initiators and effector caspases, which have been found activated in PD patients, experimental models as well as in neuronal cultures. Nitric oxide (NO) seems to be a central molecule due to its ability to modulate both pro and antiapoptotic phenomenon. The review focuses on the diverse extrinsic and intrinsic factors, signaling pathways and their modulation by NO leading to the death of dopaminergic neurons.