THE METABOLIC PATHWAY GENERATING P3, AN A-BETA-PEPTIDE FRAGMENT, IS PROBABLY NON-AMYLOIDOGENIC

被引：33
作者：
NASLUND, J
JENSEN, M
TJERNBERG, LO
THYBERG, J
TERENIUS, L
NORDSTEDT, C
机构：
[1] KAROLINSKA INST,DEPT CLIN NEUROSCI,EXPTL ALCOHOL & DRUG ADDICT RES SECT,S-17176 STOCKHOLM,SWEDEN
[2] KAROLINSKA INST,HUDDINGE UNIV HOSP,DEPT GERIATR MED,S-14186 HUDDINGE,SWEDEN
[3] KAROLINSKA INST,MED NOBEL INST,DEPT CELL & MOLEC BIOL,S-17177 STOCKHOLM,SWEDEN
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1994年 / 204卷 / 02期
关键词：
D O I：
10.1006/bbrc.1994.2527
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The Alzheimer A beta amyloid precursor protein is metabolized by at least two secretory pathways. One generates the A beta peptide and the other a N-terminally truncated A beta fragment termed p3 that is considered non-amyloidogenic. However, direct evidence is missing. We have undertaken to synthesize and purify p3. Pure p3 polymerizes in vitro, forming a lattice with an ultrastructure distinct from the linear fibrils of A beta. In contrast to amyloid, polymerized p3 does not bind thioflavine T. It is therefore concluded that amino acids in the N-terminal part of the A beta molecule are required for formation of typical amyloid fibrils and that the metabolic pathway generating p3 probably is non-amyloidogenic. (C) 1994 Academic Press, Inc.
引用
收藏
页码：780 / 787
页数：8
相关论文
共 25 条
[1]  
BURDICK D, 1992, J BIOL CHEM, V267, P546
[2]   PROCESSING OF ALZHEIMER BETA-A4 AMYLOID PRECURSOR PROTEIN - MODULATION BY AGENTS THAT REGULATE PROTEIN-PHOSPHORYLATION [J].
BUXBAUM, JD ;
GANDY, SE ;
CICCHETTI, P ;
EHRLICH, ME ;
CZERNIK, AJ ;
FRACASSO, RP ;
RAMABHADRAN, TV ;
UNTERBECK, AJ ;
GREENGARD, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (15) :6003-6006
[3]   PROTEIN-PHOSPHORYLATION INHIBITS PRODUCTION OF ALZHEIMER AMYLOID-BETA/A4 PEPTIDE [J].
BUXBAUM, JD ;
KOO, EH ;
GREENGARD, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (19) :9195-9198
[4]   RELEASE OF EXCESS AMYLOID BETA-PROTEIN FROM A MUTANT AMYLOID BETA-PROTEIN PRECURSOR [J].
CAI, XD ;
GOLDE, TE ;
YOUNKIN, SG .
SCIENCE, 1993, 259 (5094) :514-516
[5]   PROTEIN-PHOSPHORYLATION REGULATES SECRETION OF ALZHEIMER-BETA-A4 AMYLOID PRECURSOR PROTEIN [J].
CAPORASO, GL ;
GANDY, SE ;
BUXBAUM, JD ;
RAMABHADRAN, TV ;
GREENGARD, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) :3055-3059
[6]   CLEAVAGE OF AMYLOID-BETA PEPTIDE DURING CONSTITUTIVE PROCESSING OF ITS PRECURSOR [J].
ESCH, FS ;
KEIM, PS ;
BEATTIE, EC ;
BLACHER, RW ;
CULWELL, AR ;
OLTERSDORF, T ;
MCCLURE, D ;
WARD, PJ .
SCIENCE, 1990, 248 (4959) :1122-1124
[7]   ALZHEIMERS-DISEASE - INITIAL REPORT OF THE PURIFICATION AND CHARACTERIZATION OF A NOVEL CEREBROVASCULAR AMYLOID PROTEIN [J].
GLENNER, GG ;
WONG, CW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 120 (03) :885-890
[8]   10 TO 14 RESIDUE PEPTIDES OF ALZHEIMERS-DISEASE PROTEIN ARE SUFFICIENT FOR AMYLOID FIBRIL FORMATION AND ITS CHARACTERISTIC X-RAY-DIFFRACTION PATTERN [J].
GOREVIC, PD ;
CASTANO, EM ;
SARMA, R ;
FRANGIONE, B .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 147 (02) :854-862
[9]  
GOWING E, 1994, J BIOL CHEM, V269, P10987
[10]   AMYLOID BETA-PEPTIDE IS PRODUCED BY CULTURED-CELLS DURING NORMAL METABOLISM [J].
HAASS, C ;
SCHLOSSMACHER, MG ;
HUNG, AY ;
VIGOPELFREY, C ;
MELLON, A ;
OSTASZEWSKI, BL ;
LIEBERBURG, I ;
KOO, EH ;
SCHENK, D ;
TEPLOW, DB ;
SELKOE, DJ .
NATURE, 1992, 359 (6393) :322-325
123