AGING, DISEASE AND NERVE-CELL DEATH

Apoptosis, or programmed cell death, is characterized by an active autodestruction of cells. Several proteins inducing (CED-3) or preventing (CED-9) neuronal death have been described in the nematode C. elegans. There is an homology between these proteins and Bcl-2 and ICE (Interleukine-1 beta-Converting Enzyme) in vertebrates. The cascade of biochemical events leading to this active neuronal ''suicide'' is triggered by initiating factors such as genotoxicity, growth factors deprivation, cytokines (TNF alpha). As the molecular mechanisms of nerve cell death start to be understood, clinicians and neurobiologists are confronted with the difficult problem of pathological aging and neuronal death in patients with neurodegenerative disorders compared to normal aging. In order to distinguish the biochemical abnormalities underlying dysfunction of neurons during aging, neuronal loss during neurodegeneration (Parkinson's disease) and nerve cell death, we searched for morphological and biochemical signs of apoptosis in dopaminergic neurons of the substantia nigra of parkinsonian patients and controls. We found characteristic histopathological features of apoptosis in about 5% of dopaminergic neurons in the brain of patients. In addition, the presence of TNF alpha receptors and the expression of the gene bcl-2 were observed in dopaminergic neurons. Thus, apoptosis could represent the ultimate step of dopaminergic neuronal degeneration in Parkinson's disease. Whether this is also the case in other neurodegenerative diseases still remains to be proven. In brief, neurons in the human brain could be classified into three categories : those which loose slowly part of their functions but are still spared by the process of neuronal death (senescence); those which are lost more rapidly than similar effects due to aging (neurodegeneration); a small number of neurons which die rapidly through apoptosis. The consequences of such observation may be important both for neurobiologists and pharmacologists as the basic mechanisms which result in senescence, disease and death of neurons could be different.