SOLUBLE MULTIMERIC ALZHEIMER BETA(1-40) PRE-AMYLOID COMPLEXES IN DILUTE-SOLUTION

被引:87
作者
LEVINE, H
机构
[1] Department of Neurodegenerative Diseases, Parke-Davis Pharmaceutical Research Division, the Warner-Lambert Company, Ann Arbor, MI 48106-1047
关键词
GLUTARALDEHYDE; SYNTHETIC PEPTIDE; FIBRIL FORMATION MODEL; CROSS-LINKING; BOROHYDRIDE REDUCTION; SDS-PAGE; MULTIMERS; PH DEPENDENCE;
D O I
10.1016/0197-4580(95)00052-G
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Aqueous solutions of beta(1-40) peptide spontaneously associate to form pentameric/hexameric complexes that can be demonstrated by SDS-PAGE following treatment with glutaraldehyde and borohydride reduction. Under amyloidogenic conditions of pH and high peptide concentration these aggregates can further associate to form sedimentable and filterable structures with beta-sheet amyloid characteristics of Thioflavine T fluorescence. The presence of such preamyloid structures at low peptide concentration suggests a mechanism by which amyloid plaques can accrete additional material by a cooperative rather than monomeric growth. The existence of a monomer <-> multimer equilibrium may partly explain the divergence of biological consequences with respect to neurotoxicity.
引用
收藏
页码:755 / 764
页数:10
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