Altered arginine metabolism in Alzheimer's disease brains
Altered arginine metabolism in Alzheimer's disease brains
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DOI：
10.1016/j.neurobiolaging.2014.03.013
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发表时间：
2014-09-01
影响因子：
4.2
通讯作者：
Zhang, Hu
中科院分区：
文献类型：
--
作者：
Liu, Ping;Fleete, Michael S.;Zhang, Hu
L-精氨酸是一种半必需氨基酸，具有多种生物活性代谢产物。越来越多的证据表明精氨酸代谢改变在阿尔茨海默病（AD）的发病机制中的作用。本研究系统地比较了AD（平均年龄80岁）和正常（平均年龄80或60岁）病例的上级额回、海马和小脑中L-精氨酸的代谢谱。一氧化氮合酶和谷胱甘肽转移酶的活性和蛋白表达随AD和年龄的变化而发生区域特异性改变。L-精氨酸及其下游代谢物（L-瓜氨酸、L-鸟氨酸、胍丁胺、腐胺、亚精胺、精胺、谷氨酸、g-氨基丁酸和谷氨酰胺）的组织浓度也存在AD和年龄相关变化，且具有代谢物或区域特异性。这些发现表明，精氨酸代谢显着改变，在不同地区的AD大脑，因此值得进一步研究，以了解其在发病机制和/或疾病的进展。(C)2014爱思唯尔公司All rights reserved.
L-arginine is a semi-essential amino acid with a number of bioactive metabolites. Accumulating evidence suggests the implication of altered arginine metabolism in the pathogenesis of Alzheimer's disease (AD). The present study systematically compared the metabolic profile of L-arginine in the superior frontal gyrus, hippocampus, and cerebellum from AD (mean age 80 years) and normal (mean age 80 or 60 years) cases. The activity and protein expression of nitric oxide synthase and arginase were altered with AD and age in a region-specific manner. There were also AD-and age-related changes in the tissue concentrations of L-arginine and its downstream metabolites (L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate, g-aminobutyric acid, and glutamine) in a metabolite-or region-specific manner. These findings demonstrate that arginine metabolism is dramatically altered in diverse regions of AD brains, thus meriting further investigation to understand its role in the pathogenesis and/or progression of the disease. (C) 2014 Elsevier Inc. All rights reserved.