کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6805373 1433563 2014 34 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Norepinephrine provides short-term neuroprotection against Aβ1-42 by reducing oxidative stress independent of Nrf2 activation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Norepinephrine provides short-term neuroprotection against Aβ1-42 by reducing oxidative stress independent of Nrf2 activation
چکیده انگلیسی
Pathophysiological evidence correlating locus ceruleus neuron loss with increased Alzheimer's disease pathology suggests that norepinephrine (NE) is neuroprotective. Here, we evaluated the effects of NE on amyloid-β (Aβ)1-42-induced neurotoxicity and determined how NE exerts its actions in human SK-N-SH neurons. NE protected SK-N-SH cells against Aβ1-42-induced neurotoxicity only after a 4-hour treatment. The ability of NE to reduce Aβ1-42-induced neurotoxicity was independent of the adrenoceptor signaling pathway. Notably, NE downregulated Aβ1-42-mediated increases in intracellular reactive oxygen species (ROS) production. However, NE did not affect Aβ1-42-induced activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) redox signaling pathway, known to be involved in oxidative stress. Among the antioxidants tested, N-acetyl cysteine and glutathione, which are not only ROS scavengers but also thiol-reducing agents, mimicked the protective effects of NE. Consistently, Kelch-like ECH-associating protein 1 inhibitors, which activated the Nrf2 pathway, failed to decrease Aβ1-42-induced ROS generation and elicited no protection against Aβ1-42. Taken together, these findings suggest that NE could exert neuroprotective function against Aβ1-42 via redox cycling and reduction of intracellular oxidative stress regardless of downstream activation of the Nrf2 pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 35, Issue 11, November 2014, Pages 2465-2473
نویسندگان
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