ABSTRACT
APP is cleaved by at least three secretase
activities. Sequential cleavage by -secretase
followed by -secretase generates the amyloid
moiety whereas cleavage by -secretase cuts
APP within the amyloid sequence. Each of
these enzymes then becomes a target for
disease-modifying therapy. Inhibition of -
secretase or -secretase would be protective as
would enhancement of the activity of -
secretase. A huge international effort
generated a fierce race to discover -secretase,
which was finally revealed in October 1999
and re-named beta-site APP-cleaving enzyme
or BACE (Vassar et al, 1999). It is certain that
inhibitors of this enzyme will be found and
examined for therapeutic benefits. -Secretase
is a more difficult target because increasing
evidence suggests that -secretase is in fact
another AD gene – presenilin-1 (Annaert et al,
1999; De Strooper et al, 1999). Presenilin-1
also cleaves other proteins including Notch,
which is involved in haematopoesis.
