Protease Nexin 1 Immunoreactivity in Senile Plaques in Alzheimer Disease and Aged Brain
Amyloid ß -protein is deposited in senile plaques of Alzheimer and Down syndrome patient1. This ß -protein is now known to be derived from a larger precursor protein (APP) 2. However, the mechanism whereby the amyloid proteins are deposited is thus far not clarified. The recent finding that the APP contains a new domain with structural similarity to the Kunitz family of protease inhibitor3–5 has raised the possibility that an imbalance of protease-protease inhibitor interaction is involved in the aberrant degradation of APP, which may lead to formation of amyloid ß -protein. In fact, this domain does have protease inhibitor activity3, and the amount of two larger versions of APP with a protease inhibitor domain appears to be elevated in Alzheimer brain. Recently, another completely unrelated protease inhibitor, al-antichymotrypsin, was demonstrated to be closely associated with amyloid fibrils6. This fact also supports the possibility that the imbalance between protease and protease inhibitor brings about the anomalous degradation of the APP7.
KeywordsDown Syndrome Alzheimer Brain Senile Plaque Aged Brain Amyloid Protein
Unable to display preview. Download preview PDF.
- 9.D. J. Knauer, and D. D. Cunningham, Protease nexins: cell—secreted proteins which regulate extracellular serine proteases, Trends Biochem. Sci. 9: 231 (1984).Google Scholar
- 10.M. McGrogan, J. Kennedy, M. P. Li, C. Hsu, R. W. Scott, C. C. Simonsen,and J. B. Baker, Molecular cloning and expression of two forms of human protease nexin 1, Biotechnology 6: 525 (1988).Google Scholar