The histidine composition of the amyloid-β domain, but not the E1 copper binding domain, modulates β-secretase processing of amyloid-β protein precursor in Alzheimer's disease

Gough, Mallory and Blanthorn-Hazell, Sophee and Parkin, Edward T (2015) The histidine composition of the amyloid-β domain, but not the E1 copper binding domain, modulates β-secretase processing of amyloid-β protein precursor in Alzheimer's disease. Journal of Alzheimer's Disease, 43 (4). pp. 1163-1168. ISSN 1387-2877

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Abstract

Amyloid-β protein precursor (AβPP) proteolysis by β- and γ-secretases generates neurotoxic amyloid-β (Aβ)-peptides in Alzheimer's disease (AD). We have investigated the role of histidine residues within the extracellular E1 copper binding and Aβ domains of AβPP in its proteolysis. By stably expressing histidine to alanine AβPP mutant constructs in SH-SY5Y cells, we show that mutations in the E1 copper binding domain had no impact on α- or β-secretase processing. Mutation of histidine 14 within the Aβ-domain specifically down-regulated β-secretase processing without impacting on non-amyloidogenic proteolysis. Understanding how histidine 14 participates in AβPP proteolysis may reveal new intervention points for AD treatments.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Alzheimer's Disease
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2738
Subjects:
ID Code:
71595
Deposited By:
Deposited On:
03 Nov 2014 14:06
Refereed?:
Yes
Published?:
Published
Last Modified:
01 Jan 2020 09:02