Role of poly(ADP-Ribose) polymerase-1 in neurologic disorders

Cell death is a normal physiological process that plays an essential role from the beginning of embryogenesis to adulthood.^1,2 Cell death is instrumental in morphogenesis, homeostasis, and differentiation. It also plays a major role in the pathogenesis of tissue damage in diseases.^3-5 In the developing central nervous system, cell death plays an important role in growth and differentiation. Although mature neurons are among the most long-lived cell types in mammals, immature neurons die in large numbers during development, shaping and sculpting the developing brain.⁶ Neuronal cell death in developing brain is thought to be responsible for matching neuronal populations to their target areas, a process believed to be controlled by a limiting supply of target-derived growth factors⁷ and by afferent synaptic activity.^8,9 After maturation, neurons become postmitotic and lose their ability to divide. Neuronal cell death induced by pathological or traumatic insults has a deleterious effect on the central nervous system because of the inability of the tissue to repair or replace the damaged neurons. In human brain, neuronal degeneration can occur after acute insults, such as stroke and trauma, as well as during progressive adult-onset diseases such as Parkinson’s disease and Alzheimer’s disease. Excitotoxicity plays an important role in many neuropathological conditions including stroke, Parkinson’s disease, and Alzheimer’s disease.^10,11 Effective approaches to prevent or limit neuronal cell death in these diseases remain elusive due largely to an incomplete understanding of the neuronal death pathways in vivo. Despite the fact that some biochemical features of neuronal cell death have been elucidated, the key players still remain to be identified. Recently, poly(ADP-ribose) polymerase-1 (PARP-1) has been identified as a very important mediator of neuronal cell death.^12-14.