Review of apoptosis vs. necrosis of substantia nigra pars compacta in Parkinson's disease.

The discovery that melanized neurons of the pars compacta of substantia nigra (pcSN) degenerate in the midbrain of human Parkinsonians is nearly a century old, but only in this decade have we gained insights into mechanisms underlying this neuronal loss. Although it had long been assumed that pcSN neurons underwent necrosis, recent (1) in vitro studies on isolated neurons, (2) in vivo studies in animals treated with neurotoxins, and (3) postmortem study of human Parkinsonian brain provide strong evidence that pcSN cells may be lost more from apoptosis (i.e., cell suicide) than from necrosis. This paper gives some historical perspective, but focuses primarily on mechanisms involved in both necrosis and apoptosis of neurons, primarily dopaminergic, and reviews the recent literature relating to apoptosis and apoptotic factors now identified in neurons undergoing neurotoxin-induced death and in postmortem human Parkinsonian brain. The weight of evidence in favor of apoptosis and apoptotic factors in these neurons, provides us with tools needed to develop anti-apoptotic factors that can be targeted to proteins on genes, so that it may be possible to decelerate or prevent the progressive neuronal cell loss in human Parkinsonians or in humans with other neurodegenerative disorders.