Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
<mark>Journal publication date</mark> | 2015 |
---|---|
<mark>Journal</mark> | Journal of Alzheimer's Disease |
Issue number | 4 |
Volume | 43 |
Number of pages | 6 |
Pages (from-to) | 1163-1168 |
Publication Status | Published |
Early online date | 28/08/14 |
<mark>Original language</mark> | English |
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.