[Apoptosis in the nervous system]

Apoptosis (programmed cell death) is a distinct form of controlled cell degeneration, different from necrosis. It serves multiple physiological functions, such as the control of cell numbers during development, the maintenance of tissue homeostasis and the deletion of abnormal cells. Apoptosis has unique morphological and biochemical features, especially at the nuclear level, in keeping with the idea of the active participation of the cell in its own demise. Gene regulation of apoptosis shows variability among different tissues, particularly regarding the signals that trigger cell death, but shares an effector phase highly conserved accross species. In the nervous system, genes have been identified which either i) promote apoptosis: Bax, Bcl-xS, c-fos, c-jun, p75NGFR and ICE-like proteases, or ii) block apoptosis: Bcl-2 and Bcl-xL. In addition, availability of trophic factors and expression of Trk membrane receptors allow for the fine adjustement of viable cells in each neuronal population. In some diseases, neuron loss takes place via apoptosis, whether exclusively or associated with necrosis, especially when cellular insults are of moderate intensity or death occurs in areas of the brain adjacent to necrotic foci. This has been shown in excitotoxicity, X-ray injury and hypoxia-ischemia. Activation of apoptosis occurs also in some neurodegenerative diseases. Infantile spinal muscular atrophy can be the first example of a pediatric hereditary disease where a deletion in the gene of a protein which inhibits neuron apoptosis has a pathogenic role. Last, some central nervous system infections produce abnormal activation of apoptosis.