Presenilins as therapeutic targets for the treatment of Alzheimer's disease

Studies demonstrating that accumulation and aggregation of the amyloid beta protein (A beta) within the brain is likely to cause Alzheimer's disease ( AD) have provided the rationale for therapeutic strategies aimed at influen cing A beta production, aggregation and clearance. gamma -secretase catalyz es the final cleavage that releases the A beta from its precursor; therefor e, it is a potential therapeutic target for the treatment of AD. Recent dat a show that the polytopic membrane proteins presenilin 1 and presenilin 2 a re either catalytic components or essential co-factors of a membrane-bound proteolytic complex that possesses gamma -secretase activity, Although rece nt findings demonstrating that gamma -secretase inhibitors bind directly to presenilins (PSs) further support a catalytic role for PSs in gamma -secre tase cleavage, additional studies ate still needed to clarify the role of P Ss in gamma -secretase cleavage and the use of targeting PSs to reduce A be ta production.