Jeong Ji-Cheon, Kang Sung-Koo, Yoon Cheol-Ho, Seo Young-Joon, Hwang Cher-Won, Ko Jeong-Heon, Lee Young-Choon, Chang Young-Chae, Kim Cheorl-Ho
Department of Biochemistry and Internal Medicine, College of Oriental Medicine, Dongguk University, Kyungju City, Kyungbuk 780-714, Korea.
Neurochem Res. 2003 Dec;28(12):1785-92. doi: 10.1023/a:1026155321328.
Alzheimer's disease (AD) is characterized by the age-related deposition of beta-amyloid (A beta) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for A beta in the pathophysiology of AD. A beta is generated by the regulated cleavage of a = 700 amino acid A beta precursor protein (betaAPP). Full-length betaAPP can undergo proteolytic cleavage either within the A beta domain to generate secreted sbetaAPP alpha or at the N-terminal and C-terminal domain(s) of A beta to generate amyloidogenic A beta peptides. Several epidemiological studies have reported that estrogen replacement therapy protects against the development of AD in postmenopausal women. The aim of this study was to elucidate the antioxidant neuroprotective mechanism of Bombusae concretio Salicea (BC). BC was effective protectants against oxidative glutamate toxicity in the murine neuroblastoma cells (N2a) and human neuroblastoma cells (SK-N-MC). BC exhibited similar protective properties against oxidative glutamate toxicity and H2O2 toxicity. BC exhibited an antioxidant activity at approximately 20 microg/ml. BC of 5 microg/ml was ineffective in preventing the oxidative modification of LDL. The half-maximal effective concentration for BC was 16 microg/ml. These results suggested that BC supplementation in elderly men may be protective in the treatment of Alzheimer's disease (AD). We report here that treatment with BC increases the secretion of the nonamyloidogenic APP fragment, sbetaAPP alpha and decreases the secretion of A beta peptides from N2a cells and rat primary cerebrocortical neurons. These results raise the possibility that BC supplementation in elderly men may be protective in the treatment of AD.
阿尔茨海默病（AD）的特征是在易损脑区出现与年龄相关的β-淀粉样蛋白（Aβ）40/42肽聚集体沉积。多层次证据表明Aβ在AD的病理生理学中起核心作用。Aβ由一种约700个氨基酸的Aβ前体蛋白（βAPP）经调控切割产生。全长βAPP可在Aβ结构域内进行蛋白水解切割以产生分泌型sβAPPα，或在Aβ的N端和C端结构域进行切割以产生淀粉样生成性Aβ肽。多项流行病学研究报告称，雌激素替代疗法可预防绝经后女性患AD。本研究的目的是阐明蜂房（BC）的抗氧化神经保护机制。BC是小鼠神经母细胞瘤细胞（N2a）和人神经母细胞瘤细胞（SK-N-MC）中对抗氧化型谷氨酸毒性的有效保护剂。BC对氧化型谷氨酸毒性和H2O2毒性表现出相似的保护特性。BC在约20μg/ml时表现出抗氧化活性。5μg/ml的BC在预防低密度脂蛋白的氧化修饰方面无效。BC的半数有效浓度为16μg/ml。这些结果表明，老年男性补充BC可能对阿尔茨海默病（AD）的治疗具有保护作用。我们在此报告，BC处理可增加非淀粉样生成性APP片段sβAPPα的分泌，并减少N2a细胞和大鼠原代大脑皮质神经元中Aβ肽的分泌。这些结果增加了老年男性补充BC可能对AD治疗具有保护作用的可能性。
