期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1822, 期 2, 页码 130-138出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2011.10.001
关键词
Alzheimer disease; 4-Hydroxy-2-nonenal; 3-Nitrotyrosine; Oligomer; Protein carbonyl; Trisomy 21
资金
- NIH [AG-05119, HD-064993, P50 AG16573, P30 AG028383]
- University of Maryland, Baltimore, MD [HHSN275200900011C, N01-HD-9-0011]
- PRIN
Down syndrome (DS) is the most common genetic cause of intellectual disability in children, and the number of adults with DS reaching old age is increasing. By the age of 40 years, virtually all people with DS have sufficient neuropathology for a postmortem diagnosis of Alzheimer disease (AD). Trisomy 21 in DS leads to an overexpression of many proteins, of which at least two are involved in oxidative stress and AD: superoxide dismutase 1 (SOD1) and amyloid precursor protein (APP). In this study, we tested the hypothesis that DS brains with neuropathological hallmarks of AD have more oxidative and nitrosative stress than those with DS but without significant AD pathology, as compared with similarly aged-matched non-DS controls. The frontal cortex was examined in 70 autopsy cases (n = 29 control and n = 41 DS). By ELISA, we quantified soluble and insoluble A beta 40 and A beta 42, as well as oligomers. Oxidative and nitrosative stress levels (protein carbonyls, 4-hydroxy-2-trans-nonenal (HNE)-bound proteins, and 3-nitrotyrosine) were measured by slot-blot. We found that soluble and insoluble amyloid beta peptide (A beta) and oligomers increase as a function of age in DS frontal cortex. Of the oxidative stress markers, HNE-bound proteins were increased overall in DS. Protein carbonyls were correlated with A beta 40 levels. These results suggest that oxidative damage, but not nitrosative stress, may contribute to the onset and progression of AD pathogenesis in DS. Conceivably, treatment with antioxidants may provide a point of intervention to slow pathological alterations in DS. (C) 2011 Elsevier B.V. All rights reserved.
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