Premium
Proteolytic Degradation of Alzheimer's Disease Amyloid β‐Peptide by a Metalloproteinase from Microglia Cells
Author(s) -
Mentlein Rolf,
Ludwig Ralf,
Martensen Ilka
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020721.x
Subject(s) - microglia , metalloproteinase , alzheimer's disease , amyloid (mycology) , peptide , chemistry , proteolytic enzymes , matrix metalloproteinase , medicine , disease , pathology , biochemistry , inflammation , immunology , enzyme
The cerebral deposition of amyloid β‐peptide (Aβ) is a histopathological characteristic of Alzheimer's disease. Because an impaired clearance of Aβ might be involved in the disease, we investigated the proteolytic degradation of synthetic Aβ (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 Aβ. Microglia activity was considerably enhanced by stimulation with lipopolysaccharide and to a lesser extent by phorbol esters. Most of the Aβ‐degrading activity was released into the medium. By use of selective inhibitors the protease was characterized as a metalloprotease of ∼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 Aβ before polymerization.