Alzheimer amyloid β/A4 peptide binding sites and a possible 'APP-secretase' activity associated with rat brain cortical membranes

Allsop, D and Yamamoto, T and Kametani, F and Miyazaki, N and Ishii, T (1991) Alzheimer amyloid β/A4 peptide binding sites and a possible 'APP-secretase' activity associated with rat brain cortical membranes. Brain Research, 551 (1-2). pp. 1-9. ISSN 0006-8993

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Abstract

We carried out ligand binding experiments on membranes from rat brain cortical grey matter using radioiodinated beta/A4 8-17, with non-specific binding determined by the addition of 10 microM unlabelled peptide. Specific, reversible binding amounted to 60-75% of total binding and showed a clear dependence on time, temperature, pH and membrane concentration. Kinetic analyses indicated a high-affinity binding site with an apparent KD of 440 pM. However, the ligand was partly degraded with loss of the Ser8, Lys16 and Leu17 residues. Excision of the two C-terminal amino acids was inhibited by EDTA, EGTA, dithiothreitol or Zn2+ but was stimulated by Ca2+ or Mn2+. These studies demonstrate high-affinity binding sites for beta/A4 8-17 (or its derivatives) in rat brain, suggesting that this region may contain a physiologically important amino acid sequence and identify a potential membrane-associated amyloid precursor protein (APP) secretase activity.

Item Type:
Journal Article
Journal or Publication Title:
Brain Research
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1312
Subjects:
ID Code:
50846
Deposited By:
Deposited On:
08 Nov 2011 09:48
Refereed?:
Yes
Published?:
Published
Last Modified:
01 Jan 2020 07:41