An NSAID-like compound, FT-9, preferentially inhibits gamma-secretase cleavage of the amyloid precursor protein compared to its effect on amyloid precursor-like protein 1.

ABSTRACT: Inhibition of gamma-secretase cleavage of the amyloid precursor protein (APP) is a prime target for the development of therapeutics for treating Alzheimer's disease; however, complete inhibition of this activity would also impair the processing of many other proteins, including the APP homologues, amyloid precursor-like protein (APLP) 1 and 2. To prevent unwanted side effects, therapeutically useful gamma-secretase inhibitors should specifically target APP processing while sparing cleavage of other gamma-substrates. Thus, since APLP1 and APLP2 are more similar to APP than any of the other known gamma-secretase substrates and have important physiological roles in their own right, we reasoned that comparison of the effect of gamma-secretase inhibitors on APLP processing should provide a sens

SUBMITTER: Sala Frigerio C 

PROVIDER: S-EPMC4489158 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature