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Titolo:
Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome
Autore:
Nunomura, A; Perry, G; Pappolla, MA; Friedland, RP; Hirai, K; Chiba, S; Smith, MA;
Indirizzi:
Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA Case Western Reserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA Case Western Reserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA Asahikawa Med Coll, Dept Psychiat & Neurol, Asahikawa, Hokkaido 078, JapanAsahikawa Med Coll Asahikawa Hokkaido Japan 078 kawa, Hokkaido 078, Japan Univ S Alabama, Dept Pathol, Mobile, AL 36688 USA Univ S Alabama Mobile AL USA 36688 ama, Dept Pathol, Mobile, AL 36688 USA Takeda Chem Ind Ltd, Div Pharmaceut Res, Pharmaceut Res Labs I, Osaka, Japan Takeda Chem Ind Ltd Osaka Japan es, Pharmaceut Res Labs I, Osaka, Japan
Titolo Testata:
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
fascicolo: 11, volume: 59, anno: 2000,
pagine: 1011 - 1017
SICI:
0022-3069(200011)59:11<1011:NOSPAD>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN A-BETA; ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; PLAQUE-FORMATION; TRANSGENIC MICE; SENILE PLAQUES; DAMAGE; NEUROTOXICITY; A-BETA-42(43); GENERATION;
Keywords:
Alzheimer disease; amyloid-beta; Down syndrome; 8-hydroxyguanosine; nitric oxide; nitrotyrosine; oxidative damage;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Perry, G Case Western Reserve Univ, Inst Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA Case Western Reserve Univ 2085 Adelbert Rd Cleveland OH USA 44106
Citazione:
A. Nunomura et al., "Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome", J NE EXP NE, 59(11), 2000, pp. 1011-1017

Abstract

The predictable chronological sequence of pathological events in Down syndrome (DS) provides the opportunity to rigorously investigate the relationship between oxidative stress and amyloid-beta (A beta) deposition. In this study, we,report a marked accumulation of oxidized nucleic acid, 8-hydroxyguanosine (8OHG), and oxidized protein, nitrotyrosine, in the cytoplasm of cerebral neurons in DS with the levels of nucleic acid and protein oxidation paralleling each other. Relative density measurements of neuronal 8OHG immunoreactivity showed that there was a significant increase (p < 0.02) in DS (n = 22, ages 0.3-65 yr) compared with age-matched controls (n = 10, ages 0.3-64 yr). As a function of age, 8OHG immunoreactivity increased significantly in the teens and twenties (p < 0.04), while AP burden only increased after age 30 (p < 0.0001). In 9 cases of DS bearing A<beta> deposition, the extent of deposits of A beta ending at amino acid 42 (A beta 42) was actually associated with a decrease in relative 8OHG (r = -0.79, p < 0.015) while A<beta>40 was not. These findings suggest that in brains of patients with DS, increased levels of oxidative damage occur prior to the onset of A beta deposition.

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Documento generato il 24/11/20 alle ore 14:33:22