Recent insights on the pro-apoptotic phenotype elicited by presenilin 2 and its caspase and presenilinase-derived fragments.
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 Parkinson's disease. Sporadic Alzheimer's 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 Alzheimer's disease are likely of genetic origin and linked to mutations on the genes coding for the amyloid precursor protein (betaAPP) and presenilins 1 and 2. Although still discussed, the hypothesis of an implication of apoptotic cell death in Alzheimer's 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.
da Costa
Cristine Alves
CA
Institut de Pharmacologie Moléculaire et Cellulaire of Centre Nationale de la Recherche Scientifique, UMR6097 CNRS/UNSA, Sophia Antipolis, France. acosta@ipmc.cnrs.fr
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D053766:Presenilin-2
D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; D020169:Caspases; D016282:Aspartic Acid Endopeptidases; C475285:presenilinase, human