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Mentlein, R, Ludwig, R and Martensen, I (1998) Proteolytic degradation of Alzheimer's disease amyloid beta-peptide by a metalloproteinase from microglia cells. J. Neurochem. 70:721-6
The cerebral deposition of amyloid beta-peptide (A beta) is a histopathological characteristic of Alzheimer's disease. Because an impaired clearance of A beta might be involved in the disease, we investigated the proteolytic degradation of synthetic A beta (40-residue peptide) in cultures of glial cells and characterized a protease involved. Whereas rat astrocytes had a very low degradation capacity, cultivated rat microglia cells cleaved A beta. Microglia activity was considerably enhanced by stimulation with lipopolysaccharide and to a lesser extent by phorbol esters. Most of the A beta-degrading activity was released into the medium. By use of selective inhibitors the protease was characterized as a metalloprotease of approximately 200 kDa that was different from neutral endopeptidase (a neuropeptide-degrading enzyme), matrix metalloproteases, or macrophage elastase. Its activity was efficiently reduced by four hydroxamic acid-based zinc-metalloprotease inhibitors that have been shown to inhibit membrane protein secretases (disintegrins). We conclude that activated microglia cells might impair amyloid plaque formation by release of a metalloprotease that degrades soluble A beta, before polymerization.
Amyloid beta-Peptides/metabolism; Animals; Animals, Newborn; Cells, Cultured; Cerebral Cortex/cytology; Cerebral Cortex/enzymology; Cytokines/pharmacology; Humans; Kinetics; Lipopolysaccharides/pharmacology; Metalloendopeptidases/metabolism; Microglia/cytology; Microglia/drug effects; Microglia/enzymology; Peptide Fragments/metabolism; Protease Inhibitors/pharmacology; Rats; Rats, Wistar; Substrate Specificity
|Gene product||Qualifier||GO Term||Evidence Code||with/from||Aspect||Extension||Notes||Status|
|GO:0001540: beta-amyloid binding||
FIG. 6. Molecular mass determination of A/I-degrading activity from microglia-conditioned medium. Microglia cells were stimulated with LPS.
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