Recent Insights on the Pro-Apoptotic Phenotype Elicited by Presenilin 2 and its Caspase and Presenilinase-Derived Fragments

摘要

Programmed cell death (PCD) also called apoptosis, is a normal and genetically controlled event that couldrnplay, when mis-regulated, a pivotal role in the development of several neurodegenerative disorders such as Parkinson’srndisease. Sporadic Alzheimer’s disease is one of the most prominent age-related syndromes whose etiology, although stillrnunknown, could be related to biochemical or environmental causes. A few cases of Alzheimer’s disease are likely of geneticrnorigin and linked to mutations on the genes coding for the amyloid precursor protein (bAPP) and presenilins 1 and 2.rnAlthough still discussed, the hypothesis of an implication of apoptotic cell death in Alzheimer’s disease neuropathologyrnhas been recently supported by a growing body of biochemical evidences. Thus, the implication of presenilins in apoptoticrnprocesses in vitro has been well documented but the mechanisms underlying this function are still a matter of intense research.rnThe aim of this review is to focus on the mechanisms by which presenilin 2 affects the programmed cell deathrnwith special emphasis on the role of the proteolytically derived presenilin fragments generated by both presenilinase- andrncaspases. The distinct apoptotic phenotypes elicited by the two parent proteins presenilins 1 and 2 and their functionalrncross talk will be briefly discussed.