Apoptosis as a general cell death pathway in neurodegenerative diseases

Neurodegenerative processes are generally characterized by the long-lasting course of neuronal death and the selectivity of the neuronal population or brain structure involved in the lesion. Two main common forms of cell deat h that have been described in neurons as in other vertebrate tissues i.e., necrosis and apoptosis. Necrosis is the result of cellular "accidents", suc h as those occurring in tissues subjected to chemical trauma. The necrotizi ng cells swell, rupture and provoke an inflammatory response. Apoptosis, on the other hand, is dependent on the cell's "decision" to commit suicide an d die, and therefore is referred to as "programmed cell death" (PCD). The c ourse of apoptotic death is characterized by a massive morphological change , including cell shrinkage, nuclear (chromosome) condensation and DNA degra dation. Activation of PCD in an individual cell is based on its own interna l metabolism, environment, developmental background and its genetic informa tion. Such a situation occurs in most of the neurodegenerative disorders su ch as Alzheimer's, Parkinson's and Huntington's diseases and amyotrophic la teral sclerosis (ALS). In these pathological situations, specific neurons u ndergo apoptotic cell death characterized by DNA fragmentation, increased l evels of pro-apoptotic genes and "apoptotic proteins" both, in human brain and in experimental models. It is of utmost importance to conclusively dete rmine the mode of cell death in neurodegenerative diseases, because new "an ti-apoptotic" compounds may offer a means of protecting neurons from cell d eath and of slowing the rate of cell degeneration and illness progression.