Apoptosis in the mammalian nervous system: Developmental and clinical implications

Among the many regulatory steps in brain development is the process of elimination of differentiating neurons at certain stages of maturation through an intrinsic suicide program now widely known as apoptosis. Apoptosis may thus describe a cell death pathway utilized by many developing cells in the nervous system, but may also be activated as a consequence of acute or chronic pathological impulses. Such pathological impulses may include brain injury, cerebral hypoxia-ischemia and the potentials of selected drugs such as N-methyl D-aspartate (NMDA) receptor antagonists, GABA mimetics and ethanol. In recent years, there has been a great interest in mechanisms of cell death in the nervous system and apoptotic cell death has been implicated in many neurodegenerative diseases such as Alzheimer's disease, amiotrophic lateral sclerosis, Parkinsons disease and other central and peripheral nervous system disorders. Recent findings have evaluated the contribution of programmed cell death and specific gene products involved in each of these cases. A deeper understanding of these processes may lead to the discovery of strategies for slowing, reducing or arresting neuronal and glial cell death induced by injury, aging or disease.