Effect of N-homocysteinylation on physicochemical and cytotoxic properties of amyloid β-peptide.
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.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Sirus
S
Khodadadi
Gholam Hossein
GH
Riazi
Shahin
S
Ahmadian
Elham
E
Hoveizi
Oveis
O
Karima
Hassan
H
Aryapour
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology / Q000633:toxicity*; D000818:Animals; D055598:Chemical Phenomena / Q000187:drug effects; D003603:Cytotoxins / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000378:metabolism; D016716:PC12 Cells; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D051381:Rats; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D003603:Cytotoxins; D006710:Homocysteine