The biogenesis and accumulation of the beta amyloid protein (Abeta) is a key 
event in the cascade of oxidative and inflammatory processes that characterises 
Alzheimer's disease. The presenilins and its interacting proteins play a pivotal 
role in the generation of Abeta from the amyloid precursor protein (APP). In 
particular, three proteins (nicastrin, aph-1 and pen-2) interact with 
presenilins to form a large multi-subunit enzymatic complex (gamma-secretase) 
that cleaves APP to generate Abeta. Reconstitution studies in yeast and insect 
cells have provided strong evidence that these four proteins are the major 
components of the gamma-secretase enzyme. Current research is directed at 
elucidating the roles that each of these protein play in the function of this 
enzyme. In addition, a number of presenilin interacting proteins that are not 
components of gamma-secretase play important roles in modulating Abeta 
production. This review will discuss the components of the gamma-secretase 
complex and the role of presenilin interacting proteins on gamma-secretase 
activity.