Active glycation in neurofibrillary pathology of Alzheimer disease: N-epsilon-(carboxymethyl) lysine and hexitol-lysine

Citation
Rj. Castellani et al., Active glycation in neurofibrillary pathology of Alzheimer disease: N-epsilon-(carboxymethyl) lysine and hexitol-lysine, FREE RAD B, 31(2), 2001, pp. 175-180
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN journal
0891-5849 → ACNP
Volume
31
Issue
2
Year of publication
2001
Pages
175 - 180
Database
ISI
SICI code
0891-5849(20010715)31:2<175:AGINPO>2.0.ZU;2-W
Abstract
Advanced glycation end products are a diverse class of posttranslational mo difications, stemming from reactive aldehyde reactions, that have been impl icated in the pathogenesis of a number of degenerative diseases. Because ad vanced glycation end products are accelerated by, and result in formation o f, oxygen-derived free radicals, they represent an important component of t he oxidative stress hypothesis of Alzheimer disease (AD). In this study, we used in situ techniques to assess N-epsilon-(Carboxymethyl)lysine (CML), t he predominant advanced glycation end product that accumulates in vivo, alo ng with its glycation-specific precursor hexitol-lysine, in patients with A D as well as in young and aged-matched control cases. Both CML and hexitol- lysine were increased in neurons, especially those containing intracellular neurofibrillary pathology in cases of AD. The increase in hexitol-lysine a nd CML in AD suggests that glycation is an early event in disease pathogene sis. In addition, because CML can result from either lipid peroxidation or advanced glycation, while hexitol-lysine is solely a product of glycation, this study, together with studies demonstrating the presence of 4-hydroxy-2 -nonenal adducts and pentosidine, provides evidence of two distinct oxidati ve processes acting in concert in AD neuropathology. Our findings support t he notion that aldehyde-mediated modifications, together with oxyradical-me diated modifications, are critical pathogenic factors in AD. (C) 2001 Elsev ier Science Inc.