Human brain beta-secretase contains heparan sulfate glycoconjugates

被引：5

作者：

Matsumoto, A

Matsumoto, R

Enomoto, T

Baba, H

机构：

[1] OSAKA TEISHIN HOSP,DEPT INTERNAL MED 1,OSAKA 543,JAPAN

[2] KOBE UNIV,SCH MED,DEPT INTERNAL MED 3,KOBE 650,JAPAN

来源：

NEUROSCIENCE LETTERS | 1996年 / 211卷 / 02期

关键词：

serine protease; beta-secretase; beta-amyloid; heparan sulfate; Alzheimer's disease; negative charge; extracellular matrix;

D O I：

10.1016/0304-3940(96)12723-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A polyclonal antibody against the 68 kDa beta-secretase was established, which recognizes a single 68 kDa band in brain homogenate of Alzheimer's disease patients and normal aged. Western analysis revealed that the protease is an acidic glycoprotein with negative charge on its glycoconjugate(s). Sensitiveness to heparitinase and glycopeptidase A indicates that the protease contains asparagine-linked oligosaccharide with heparan sulfate moieties. Specific detection of the 68 kDa band in the analysis using anti-heparan sulfate antibody, and its Lime-course-dependent degradation, also confirm the above results. It seems that, like human blood coagulation factors IXa and XIa, the glycoconjugate(s) attached to the protease interfere with substrate specificity, stability and topological restriction of proteolysis in brain extracellular matrix, where diffuse plaque formation is taking place.

引用

页码：105 / 108

页数：4

共 20 条

[11] LEVOUGLE B, 1994, NEUROREPORT, V5, P1389
[12] ABERRANT PROTEOLYSIS OF THE BETA-AMYLOID PRECURSOR PROTEIN IN FAMILIAL ALZHEIMERS-DISEASE LYMPHOBLASTOID-CELLS
MATSUMOTO, A
FUJIWARA, Y
[J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 217 (01): : 21 - 27
[13] A SERINE-PROTEASE IN ALZHEIMERS-DISEASE CELLS CLEAVES A 16K-PEPTIDE WITH FLANKING RESIDUES UPSTREAM TO BETA-AMYLOID-N-TERMINUS AS NATURAL SUBSTRATE
MATSUMOTO, A
MATSUMOTO, R
BABA, H
FUJIWARA, Y
[J]. NEUROSCIENCE LETTERS, 1995, 195 (03) : 171 - 174
[14] CA2+-DEPENDENT 68-KILODALTON PROTEASE IN FAMILIAL ALZHEIMERS-DISEASE CELLS CLEAVES THE N-TERMINUS OF BETA-AMYLOID
MATSUMOTO, A
FUJIWARA, Y
[J]. BIOCHEMISTRY, 1994, 33 (13) : 3941 - 3948
[15] MOLECULAR-CLONING OF HUMAN CDNA WITH A SEQUENCE HIGHLY SIMILAR TO THAT OF THE DIHYDROFOLATE-REDUCTASE GENE IN BRAIN LIBRARIES DERIVED FROM ALZHEIMERS-DISEASE PATIENTS
MATSUMOTO, A
MATSUMOTO, R
FUJIWARA, Y
[J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1995, 230 (01): : 337 - 343
[16] FAMILIAL ALZHEIMERS-DISEASE CELLS ABNORMALLY ACCUMULATE BETA-AMYLOID-HARBORING PEPTIDES PREFERENTIALLY IN CYTOSOL BUT NOT IN EXTRACELLULAR FLUID
MATSUMOTO, A
MATSUMOTO, R
[J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1994, 225 (03): : 1055 - 1062
[17] SULFATED GLYCOSAMINOGLYCANS AND DYES ATTENUATE THE NEUROTOXIC EFFECTS OF BETA-AMYLOID IN RAT PC12 CELLS
POLLACK, SJ
SADLER, IIJ
HAWTIN, SR
TAILOR, VJ
SHEARMAN, MS
[J]. NEUROSCIENCE LETTERS, 1995, 184 (02) : 113 - 116
[18] NORMAL AND ABNORMAL BIOLOGY OF THE BETA-AMYLOID PRECURSOR PROTEIN
SELKOE, DJ
[J]. ANNUAL REVIEW OF NEUROSCIENCE, 1994, 17 : 489 - 517
[19] LOCALIZATION OF HEPARAN-SULFATE GLYCOSAMINOGLYCAN AND PROTEOGLYCAN CORE PROTEIN IN AGED BRAIN AND ALZHEIMERS-DISEASE
SU, JH
CUMMINGS, BJ
COTMAN, CW
[J]. NEUROSCIENCE, 1992, 51 (04) : 801 - 813
[20] AMYLOID-BETA PROTEIN-PRECURSOR GENE AND HEREDITARY CEREBRAL-HEMORRHAGE WITH AMYLOIDOSIS (DUTCH)
VAN BROECKHOVEN, C
HAAN, J
BAKKER, E
HARDY, JA
VANHUL, W
WEHNERT, A
VEGTERVANDERVLIS, M
ROOS, RAC
[J]. SCIENCE, 1990, 248 (4959) : 1120 - 1122

← 1 2 →