The Role of Presenilin and its Interacting Proteins in the Biogenesis of Alzheimer's Beta Amyloid
Computing, Health and Science
Exercise, Biomedical and Health Science
The biogenesis and accumulation of the beta amyloid protein (Ab) 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 Ab 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 (c-secretase) that cleaves APP to generate Ab. Reconstitution studies in yeast and insect cells have provided strong evidence that these four proteins are the major components of the c-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 c-secretase play important roles in modulating Ab production. This review will discuss the components of the c-secretase complex and the role of presenilin interacting proteins on c-secretase activity.