Cristine A da Costa Pages 507 - 514 ( 8 )
Programmed cell death (PCD) also called apoptosis, is a normal and genetically controlled event that could play, when mis-regulated, a pivotal role in the development of several neurodegenerative disorders such as Parkinsons disease. Sporadic Alzheimers disease is one of the most prominent age-related syndromes whose etiology, although still unknown, could be related to biochemical or environmental causes. A few cases of Alzheimers disease are likely of genetic origin and linked to mutations on the genes coding for the amyloid precursor protein (bAPP) and presenilins 1 and 2. Although still discussed, the hypothesis of an implication of apoptotic cell death in Alzheimers disease neuropathology has been recently supported by a growing body of biochemical evidences. Thus, the implication of presenilins in apoptotic processes in vitro has been well documented but the mechanisms underlying this function are still a matter of intense research. The aim of this review is to focus on the mechanisms by which presenilin 2 affects the programmed cell death with special emphasis on the role of the proteolytically derived presenilin fragments generated by both presenilinase- and caspases. The distinct apoptotic phenotypes elicited by the two parent proteins presenilins 1 and 2 and their functional cross talk will be briefly discussed.
Alzheimer's disease, presenilins, presenilinase, caspases, apoptosis
Institut de Pharmacologie Moleculaire et Cellulaire of Centre Nationale de la Recherche Scientifique,UMR6097 CNRS/UNSA, 660 route des Lucioles, Sophia Antipolis, 06560, France.