Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity

Nobuya Kitaguchi, Yasuyuki Takahashi, Yasuo Tokushima, Satoshi Shiojiri, Hirataka Ito

Research output: Contribution to journalArticle

854 Citations (Scopus)

Abstract

Alzheimer's disease 1 is characterized by cerebral deposits of amyloid β-protein (AP) as senile plaque core and vascular amyloid 2-6 , and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain 7-11 . 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 a mi no acids at the N-terminal of the protein deduced from this insert is highly homologous to the basic trypsin inhibitor family 12 , 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.

Original languageEnglish
Pages (from-to)530-532
Number of pages3
JournalNature
Volume331
Issue number6156
DOIs
Publication statusPublished - 01-01-1988

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Amyloidogenic Proteins
Protein Precursors
Alzheimer Disease
Peptide Hydrolases
Complementary DNA
Nucleotides
Trypsin Inhibitors
COS Cells
Amyloid Plaques
Brain
Alternative Splicing
Glioblastoma
Gene Library
DNA Sequence Analysis
Amyloid
Trypsin
Blood Vessels
Exons
Proteins
Cell Line

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kitaguchi, Nobuya ; Takahashi, Yasuyuki ; Tokushima, Yasuo ; Shiojiri, Satoshi ; Ito, Hirataka. / Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. In: Nature. 1988 ; Vol. 331, No. 6156. pp. 530-532.
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Kitaguchi, N, Takahashi, Y, Tokushima, Y, Shiojiri, S & Ito, H 1988, 'Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity', Nature, vol. 331, no. 6156, pp. 530-532. https://doi.org/10.1038/331530a0

Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. / Kitaguchi, Nobuya; Takahashi, Yasuyuki; Tokushima, Yasuo; Shiojiri, Satoshi; Ito, Hirataka.

In: Nature, Vol. 331, No. 6156, 01.01.1988, p. 530-532.

Research output: Contribution to journalArticle

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