Degradation of amyloid beta-protein by a serine
protease-alpha2-macroglobulin complex.
Qiu WQ, Borth W, Ye Z,
Haass C, Teplow DB, Selkoe DJ. Degradation of amyloid beta-protein
by a serine protease-alpha2-macroglobulin complex. 1: J Biol Chem.
1996 Apr 5;271(14):8443-51.
Progressive cerebral
deposition of the amyloid beta-peptide (Abeta) is an early and
constant feature of Alzheimer's disease. Abeta is derived by
proteolysis from the beta-amyloid precursor protein. beta-Amyloid
precursor protein processing and the generation of Abeta have been
extensively characterized, but little is known
about the mechanisms of
degradation of this potentially neurotoxic peptide.
We identified and purified
a proteolytic activity in culture medium that can degrade secreted
Abeta but not larger proteins in the medium. Detection of the
activity in conditioned medium required the presence of fetal bovine
serum and the passage of the cells with a pancreatic trypsin
preparation. Its inhibitor profile showed
that the activity was a
serine protease other than trypsin or chymotrypsin. The protease
occurs as a stable approximately 700-kDa complex with the inhibitor,
alpha2-macroglobulin (alpha2M), that retains activity against small
substrates such as Abeta.
Its NH2-terminal sequence
suggests that the protease is previously unidentified. Our results
indicate that the Abeta-degrading protease we have detected is a
non-trypsin component of a pancreatic trypsin preparation or else
derives from a zymogen in serum that is activated by a protease in
the latter preparation. Because Abeta-bearing plaques in Alzheimer's
disease brain contain both alpha2M and receptors of alpha2M-protease
complexes, the same or a similar alpha2M-protease complex could
arise in vivo and play a role in Abeta clearance.
External Link: PMID:
8626544