Site-specific glycation of A1-42 affects fibril formation and is neurotoxic
Jin Ng, Harveen Kaur, Thomas Collier, Kevin Chang, Anna ES Brooks, Jane R Allison, Margaret A Brimble, Anthony Hickey, Nigel P Birch
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2019
Aβ1-42 is involved in Alzheimer's disease (AD) pathogenesis and is prone to glycation, an irreversible process where proteins accumulate advanced glycated end products (AGEs). Nϵ-(Carboxyethyl)lysine (CEL) is a common AGE associated with AD patients and occurs at either Lys-16 or Lys-28 of Aβ1-42. Methyglyoxal is commonly used for the unspecific glycation of Aβ1-42, which results in a complex mixture of AGE-modified peptides and makes interpretation of a causative AGE at a specific amino acid residue difficult. We address this issue by chemically synthesizing defined CEL modifications on Aβ1-42 at Lys-16 (Aβ-CEL16), Lys-28 (Aβ-CEL28), and Lys-16 and -28 (Aβ-CEL16&28). We demonstrated that do..View full abstract
This work was supported by grants from Brain Research New Zealand Rangahau Roro Aotearoa, the University of Auckland Faculty Research Development Fund, the Lottery Grants Board. The authors declare that they have no conflicts of interest with the contents of this article.