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

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.

journal_name

Brain Res

journal_title

Brain research

authors

Allsop D,Yamamoto T,Kametani F,Miyazaki N,Ishii T

doi

10.1016/0006-8993(91)90905-b

subject

Has Abstract

pub_date

1991-06-14 00:00:00

pages

1-9

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

0006-8993(91)90905-B

journal_volume

551

pub_type

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