Journal article

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

Abstract

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..

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University of Melbourne Researchers