Gp. Lim et al., MATRIX METALLOPROTEINASES IN DOG BRAINS EXHIBITING ALZHEIMER-LIKE CHARACTERISTICS, Journal of neurochemistry, 68(4), 1997, pp. 1606-1611
We have previously reported that the amount of the neuronal matrix met
alloproteinase (MMP) MMP-9, capable of cleaving beta-amyloid(1-40) pre
dominantly at Leu(34)-Met(35), is increased in a latent form in hippoc
ampal specimens from AD patients and have suggested that the lack of a
ctivation of this enzyme may contribute to the deposition of beta-amyl
oid in plaques. The current study addresses whether similar matrix pro
teinases are detectable in amyloid-positive and -negative brain specim
ens of aged beagles. Using quantitative zymography, three major neutra
l proteinases with molecular masses of 60, 95, and 280 kDa were readil
y detected. These enzymes have the characteristics of MMPs because the
y were inhibited by EDTA and 1,10-phenanthroline, and their activities
were restored by addition of both Ca2+ and Zn2+. The 95- and 280-kDa
proteinases cross-reacted with specific monoclonal antibodies to human
MMP-9 (gelatinase B; EC 3.4.24.35). Canine MMP-9 was latent because a
ctivation by organomercurial treatment resulted in a characteristic de
crease in molecular mass. Statistical analysis revealed no difference
in the 60-kDa proteinase activity in amyloid-positive and -negative br
ain specimens. However, significantly increased amounts of latent MMP-
9 were observed in amyloid-positive brain specimens (p less than or eq
ual to 0.05) compared with amyloid-negative brain specimens. The obser
vations document that changes in MMP-9 expression in amyloid-positive
beagle brains are similar to those reported in the human Alzheimer's d
isease hippocampus and suggest the possibility that insufficient activ
ation of MMP-9 may contribute to beta-amyloid accumulation, a hypothes
is that needs to be further investigated.