Apoptosis and its Role in Parkinson’s Disease

ABSTRACT

Parkinson’s disease is one of the most common neurodegenerative dis­eases in the elderly. The motor symptoms occur predominantly due to substantial dopamine depletion, caused by degeneration of the dopaminergic neurons in substantia nigra pars compacta. Apoptosis has been implicated as the main mechanism of neuronal death in Parkinson’s disease. Apoptosis is mediated by a number of initiator and executioner caspases, and occurs via the intrinsic or extrinsic pathways. Activation of initiator caspase-9 mediates the intrinsic pathway—also called the mitochondria-mediated pathway. Alternatively, activa­tion of initiator caspase-8 mediates the extrinsic apoptotic pathway—the cell death receptor–mediated pathway. Both initiator caspases converge onto a com­mon pathway of executioner caspases, involving caspase-3 and caspase-6. Activation of the executioner caspases leads to the morphological features characteristic of apoptosis, such as DNA cleavage and its subsequent fragmenta­tion. Proapoptotic factors, such as Bax, have been implicated in neuronal cell death in Parkinson’s disease, and there is evidence that both the intrinsic and extrinsic apoptotic pathways may play a role. This chapter provides an overview of apoptosis and its significance in Parkinson’s disease.