Effect of N-homocysteinylation on physicochemical and cytotoxic properties of amyloid β-peptide

FEBS Lett. 2012 Jan 20;586(2):127-31. doi: 10.1016/j.febslet.2011.12.018. Epub 2011 Dec 23.


Abstract Hyperhomocysteinemia has recently been identified as an important risk factor for Alzheimer's disease (AD). One of the potential mechanisms underlying harmful effects of homocysteine (Hcy) is site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HCTL). The accumulation of amyloid β-peptide (Aβ) in the brain is a neuropathological hallmark of AD. In the present study we were interested to investigate the effects of N-homocysteinylation on the aggregation propensity and neurotoxicity of Aβ(1-42). By coupling several techniques, we demonstrated that the homocysteinylation of lysine residues increase the neurotoxicity of the Aβ peptide by stabilizing soluble oligomeric intermediates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / physiology
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Chemical Phenomena / drug effects
  • Cytotoxins / metabolism
  • Homocysteine / metabolism*
  • Homocysteine / physiology
  • Humans
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / metabolism
  • PC12 Cells
  • Protein Multimerization
  • Protein Processing, Post-Translational / physiology*
  • Rats
  • Structure-Activity Relationship


  • Amyloid beta-Peptides
  • Cytotoxins
  • Homocysteine