Molecular Biology of Dopamine-Induced Apoptosis

The causes for the highly selective loss of dopaminergic neurons in the substantia nigra pars compacta in Parkinson’s disease (PD) are still unknown. However, a major advance has been recently made with the introduction of the concept of apoptosis as the route leading this specific neuronal population to degeneration. Apoptosis, or programmed cell death (PCD), is an active, controlled program inherent in every living cell. Upon receiving certain signals, cells that are destined to die undergo a highly characteristic process of “suicide.” This process consists of massive biochemical and morphological alterations, including cell shrinkage, loss of cell-to-cell contacts, blebbing of cell membranes, cytoskeletal rearrangements, and DNA condensation and fragmentation. It culminates in cell conversion to membrane-bound particles (apoptotic bodies) that are ready to be digested by neighboring macrophages (1 –3 ).