Abstract
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.
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References
C. L. Masters, G. Simms, N. Weinmann, G. Multhaup, B. L. McDnard, and K. Beyreuther, Amyloid plaque core protein in Alzheimer’s disease and Down’s syndrome, Pro. Natl. Acad. Sci. USA 82: 4245 (1985).
J. Kang, H. G. Lamaire, A. Unterbeck, J. M. Salbaum, C. L. Masters, K. H. Grzeschik, G. Multhaup, K. Beyreuther, and B. Muller—hill, The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell surface receptor, Nature 325: 733 (1987).
N Kitaguchi, Y. Takahashi, Y. Tokushima, S. Shiojiri, and H. Ito, Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity, Nature 331: 530 (1988).
P. Ponte, P. Gonzales—Dewhitt, J. Schilling, J. Miller, D. Hsu, B. Greenberg, K. Davis, W. Wallance, I. Lieberg, F. Fuller, and B. Cordell, A new A4 amyloid mRNA contains a domain homologous to serine protease inhibitors, Nature 331: 525 (1988).
R. E. Tanzi, A. I. McClatchey, E. D. Lamperti, L. Villa—Komarff, J. F. Gusella, and R. L. Neve, Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer’s disease, Nature 331: 528 (1988).
C. R. Abraham, D. J. Selkoe, and H. Potter, Immunochemical identification of the serine protease inhibitor al—antichymotrypsin in the brain amyloid deposits of Alzheimer’s disease, Cell 52: 487 (1988).
C. R. Abraham, C. Richards, and J. Gauldie, Alzheimer’s disease: recent advances in understanding the brain amyloid deposits, Biotechnology 7: 147 (1989).
J. B. Baker, D. A. Low, R. L. Simmer, and D. D. Cunningham, Protease nexin: A cellular component that links thrombin and plasminogen activator and mediates their binding to cells, Cell 21: 37 (1980).
D. J. Knauer, and D. D. Cunningham, Protease nexins: cell—secreted proteins which regulate extracellular serine proteases, Trends Biochem. Sci. 9: 231 (1984).
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).
D. Monard, Cell—derived proteases and protease inhibitors as regulators of neurite outgrowth, Trends Neurosci. 11: 525 (1988).
D. H. Farrell, W. E. Nostrand, and D. D. Cunningham, A simple two—step purification of protease nexin, Biochem. J. 237: 907 (1986).
E. W. Howard, and D. J. Knauer, Human protease nexin-1, J. Biol. Chem. 261: 684 (1986).
R. W. Scott, B. L. Bergman, A. Bajpai, R. Hersh, H. Rodrigues, B. Jones, C. Barreda, S. Watts, and J. B. Baker, Protease nexin. Properties and a modified purification procedure, J. Biol. Chem. 260: 7029 (1985).
S. Gloor, K. Odink, J. Guenther, H. Nick, and D. Monard, A. Glia—derived neurite promoting factor with protease inhibitory activity belongs to the protease nexin, Cell 47: 687 (1986).
D. J. Knauer, K. M. Scaparro, and D. D. Cunningham, The gamma subunit of 7S nerve growth factor binds to cells via complexes formed with two cell—secreted nexins, J. Biol. Chem. 257: 15098 (1982).
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© 1990 Plenum Press, New York
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Namba, Y., Ikeda, K., Tomonaga, M. (1990). Protease Nexin 1 Immunoreactivity in Senile Plaques in Alzheimer Disease and Aged Brain. In: Nagatsu, T., Fisher, A., Yoshida, M. (eds) Basic, Clinical, and Therapeutic Aspects of Alzheimer’s and Parkinson’s Diseases. Advances in Behavioral Biology, vol 38A. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5844-2_11
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DOI: https://doi.org/10.1007/978-1-4684-5844-2_11
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