A role for extracellular matrix degradation and matrix metalloproteinases in senile dementia?
In brain as in cartilage, the extracellular matrix contains aggregates formed by hyaluronic acid (HA) and proteoglycans. In osteoarthritic cartilage, release of the proteoglycans from the aggregates by cleavage of the HA-binding region results in the accumulation of the HA-binding region and in the fragmentation of the released proteoglycans. Stromelysin, a matrix neutral metalloproteinase, is one of the enzymes responsible for the cleavage of the HA-binding region. We suggest that a similar process also occurs in senile dementia. The brain proteoglycan contains sequences identical to those of aggrecan, which are recognized and cleaved by stromelysin, and is, in fact, susceptible to stromelysin digestion. Monoclonal antibodies reacting with glial HA-binding protein, but not with the parent protein, stained several senile plaques as defined by their reactivity with antibodies to the amyloid-beta protein in double-labeling experiments.
Bignami
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Research and Development Service (151), Department of Veterans Affairs Medical Center, West Roxbury, MA 02132.
LeBlanc
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Perides
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D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000911:Antibodies, Monoclonal; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans; D003704:Dementia / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D014018:Tissue Distribution; D053675:Versicans
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C508322:VCAN protein, human; D053675:Versicans; D008666:Metalloendopeptidases