Abstract:
:Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently binds amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated to be intimately associated with pathological lesions of Alzheimer's disease (AD), suggesting that oxidative stress is a major component in the disease. Here, we examined the HNE-cross-linking modifications by using an antibody specific for a lysine-lysine cross-link. Since in a prior study we noted no immunolabeling of neuritic plaques or neurofibrillary tangles but instead found strong labeling of axons, we focused this study on axons. Axonal labeling was examined in mouse sciatic nerve, and immunoblotting showed the cross-link was restricted to neurofilament heavy and medium subunits, which while altering migration, did not indicate larger NF aggregates, indicative of intermolecular cross-links. Examination of mice at various ages showed the extent of modification remaining relatively constant through the life span. These findings demonstrate lipid-cross-linking peroxidation primarily involves lysine-rich neurofilaments and is restricted to intramolecular cross-links.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Perry EA,Castellani RJ,Moreira PI,Nunomura A,Lui Q,Harris PL,Sayre LM,Szweda PA,Szweda LI,Zhu X,Smith MA,Perry Gdoi
10.3109/10715762.2013.794265subject
Has Abstractpub_date
2013-07-01 00:00:00pages
507-10issue
6-7eissn
1071-5762issn
1029-2470journal_volume
47pub_type
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