Site-specific glycation of Aβ1-42 affects fibril formation and is neurotoxic.

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). N^ϵ-(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 double-CEL glycations at Lys-16 and Lys-28 of Aβ1-42 had the most profound impact on

SUBMITTER: Ng J 

PROVIDER: S-EPMC6552435 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature