Epitopes described in "Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations."

Article Authors:Quan Liu; Mark A Smith; Jesus Avilá; John DeBernardis; Mayank Kansal; Atsushi Takeda; Xiongwei Zhu; Akihiko Nunomura; Kazuhiro Honda; Paula I Moreira; Catarina R Oliveira; Maria S Santos; Shun Shimohama; Gjumrakch Aliev; Jack de la Torre; Hossein A Ghanbari; Sandra L Siedlak; Peggy L R Harris; Lawrence M Sayre; George Perry
Article Title:Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations.
Reference Detail
Reference ID:1014424
Abstract:Several recent studies support a link between tau protein phosphorylation and adduction of tau by reactive carbonyls. Indeed, the phosphorylation-dependent adduction of tau by carbonyl products resulting from lipid peroxidation creates the neurofibrillary tangle-related antigen, Alz50. To determine whether epitopes of carbonyl-modified tau are major conformational changes associated with neurofibrillary tangle formation, we examined seven distinct antibodies raised against neurofibrillary tangles that recognize unique epitopes of tau in Alzheimer disease. Consistently, all seven antibodies recognize tau more strongly (4- to 34-fold) after treatment of normal tau with the reactive carbonyl, 4-hydroxy-2-nonenal (HNE), but only when tau is in the phosphorylated state. These findings not only support the idea that oxidative stress is involved in neurofibrillary tangle formation occurring in brains of Alzheimer disease patients, but also show, for the first time, that HNE modifications of tau promote and contribute to the generation of the major conformational properties defining neurofibrillary tangles.
Affiliations:Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Reference Type:Literature
PubMed ID:15721985
Journal:Free Radic Biol Med
Journal Volume:38
Article Pages:746-54
Journal ISSN:0891-5849
Article Chemical List:Aldehydes;Epitopes;tau Proteins;4-hydroxy-2-nonenal
Article MeSH List:Aged; Aged, 80 and over; Aldehydes(chemistry); Alzheimer Disease(immunology; metabolism); Animals; Epitopes(chemistry); Humans; Immunohistochemistry; Lipid Peroxidation; Mice; Models, Genetic; Oxidative Stress; Phosphorylation; Protein Conformation; Time Factors; tau Proteins(chemistry; metabolism)
Curation Last Updated:2016-04-05 22:42:28