Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity
- PMID: 2893291
- DOI: 10.1038/331530a0
Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity
Abstract
Alzheimer's disease is characterized by cerebral deposits of amyloid beta-protein (AP) as senile plaque core and vascular amyloid, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain. From a cDNA library of a human glioblastoma cell line, we have isolated a cDNA identical to that previously reported, together with a new cDNA which contains a 225-nucleotide insert. The sequence of the 56 amino acids at the N-terminal of the protein deduced from this insert is highly homologous to the basic trypsin inhibitor family, and the lysate from COS-1 cells transfected with the longer APP cDNA showed an increased inhibition of trypsin activity. Partial sequencing of the genomic DNA encoding APP showed that the 225 nucleotides are located in two exons. At least three messenger RNA species, apparently transcribed from a single APP gene by alternative splicing, were found in human brain. We suggest that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism.
Similar articles
-
Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.Nature. 1988 Feb 11;331(6156):528-30. doi: 10.1038/331528a0. Nature. 1988. PMID: 2893290
-
A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors.Nature. 1988 Feb 11;331(6156):525-7. doi: 10.1038/331525a0. Nature. 1988. PMID: 2893289
-
The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II.Nature. 1989 Sep 14;341(6238):144-7. doi: 10.1038/341144a0. Nature. 1989. PMID: 2506449
-
The amyloid peptide precursor in Alzheimer's disease.Acta Neurol Belg. 1995 Dec;95(4):197-209. Acta Neurol Belg. 1995. PMID: 8553793 Review.
-
The beta amyloid protein precursor: mRNAs, membrane-associated forms, and soluble derivatives.Prog Clin Biol Res. 1989;317:971-84. Prog Clin Biol Res. 1989. PMID: 2513588 Review.
Cited by
-
Interleukin-1 stimulates the beta-amyloid precursor protein promoter.Cell Mol Neurobiol. 1990 Dec;10(4):485-95. doi: 10.1007/BF00712843. Cell Mol Neurobiol. 1990. PMID: 2091832
-
Differential brain expression of the Alzheimer's amyloid precursor protein.EMBO J. 1989 Dec 1;8(12):3627-32. doi: 10.1002/j.1460-2075.1989.tb08536.x. EMBO J. 1989. PMID: 2583112 Free PMC article.
-
The molecular pathology of amyloid deposition in Alzheimer's disease.Mol Neurobiol. 1991;5(2-4):389-98. doi: 10.1007/BF02935560. Mol Neurobiol. 1991. PMID: 1823142 Review. No abstract available.
-
Arginine specific endopeptidases modify the aggregation properties of a synthetic peptide derived from Alzheimer beta/A4 amyloid.Neurochem Res. 1992 Apr;17(4):367-74. doi: 10.1007/BF00974579. Neurochem Res. 1992. PMID: 1513420
-
Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway.J Cell Biol. 1993 Apr;121(2):295-304. doi: 10.1083/jcb.121.2.295. J Cell Biol. 1993. PMID: 8468348 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
