CER on CAM Antioxidant Therapies (CERCAT)

该计划项目设在莱纳斯·鲍林研究所，这是一家新兴的微量营养素和抗氧化剂研究和教育的国际领导者，也是美国少数几个完全专注于通过饮食和CAM方法促进健康和预防疾病的中心之一。补充和替代医学(CAM)抗氧化剂疗法卓越研究中心(CERCAT)将研究两类特定的CAM抗氧化剂：(I)调节细胞氧化还原环境从而调节细胞信号和转录激活的抗氧化剂，例如通过影响具有低PKA的关键硫醇或上调内源性抗氧化剂系统。由此研究的CAM抗氧化剂 类别包括二硫醇化合物(如α-碘酸)和金属螯合剂(如乙二胺四乙酸乙二酯和去铁胺)。(Ii)能抑制过氧亚硝酸根和其他活性氮物种硝化酪氨酸的高共轭或芳香族化合物。在这一类中要检查的主要抗氧化剂是尿酸。利用细胞培养研究和相关的动物模型，CERCAT将确定这些CAM抗氧化剂的分子和细胞作用机制，以及它们在治疗肌萎缩侧索硬化症(ALS)和心血管疾病(CVD)以及逆转细胞对衰老造成的压力抵抗力丧失方面的安全性和有效性。CERCAT的这些目标得到了NCCAM“更加重视对CAM方法基础机制的研究”和其“2003财年研究重点”的“生物学研究”的支持。 EDTA螯合疗法在CVD动物模型和神经退行性疾病中的应用。CERCAT的研究目标将通过三个高度互动的项目来实现：1)“内皮功能和心血管疾病中的金属螯合剂和硫醇”(Balz Frei)；2)“通过硫辛酸治疗降低对毒素的易感性”(Tory Hagen)；以及3)“CAM抗氧化剂和肌萎缩侧索硬化”(Joseph Beckman)。中心调查人员将得到一个行政核心的协助，该核心负责处理预算、报告和外部咨询需求。总之，CERCAT将调查CAM抗氧化剂在肌萎缩侧索硬化症、心血管疾病和衰老中的有效性，并提供关于潜在机制、剂量反应效应和相关生物靶点的基本知识，以推动这些CAM疗法进入人体试验；同样重要的是，这些研究将测试可能阻碍CAM抗氧化剂进入人体试验的不良影响。

This Program Project is based in the Linus Pauling Institute, an emerging international leader in research and education on micronutrients and antioxidants, and one of a few centers in the US to focus entirely on health promotion and disease prevention by dietary and CAM approaches. The Center of Excellence for Research on Complementary and Alternative Medicine (CAM) Antioxidant Therapies (CERCAT) will investigate two specific categories of CAM antioxidants: (i) Antioxidants that modulate the cellular redox environment and, thus, cell signaling and transcriptional activation, e.g. by affecting critical thiols with a low pKa or upregulating endogenous antioxidant systems. The CAM antioxidants to be investigated from this category are dithiol compounds (e.g. alpha-Iipoic acid) and metal chelators (e.g. EDTA and desferrioxamine). (ii) Highly conjugated or aromatic compounds that inhibit tyrosine nitration by peroxynitrite and other reactive nitrogen species. The principal antioxidant to be examined in this category is uric acid. Using cell culture studies and relevant animal models, CERCAT will determine the molecular and cellular mechanisms of action of these CAM antioxidants, and their safety and efficacy in treating amyotrophic lateral sclerosis (ALS) and cardiovascular diseases (CVD) and reversing the loss of cellular resistance to stress that occurs with aging. These goals of CERCAT are buttressed by NCCAM's "increased emphasis on studies of the mechanism underlying CAM approaches" and its "FY 2003 Research Priorities" of "studies of the biology of EDTA chelation therapy in animal models of CVD" and "neurodegenerative disorders using in vitro studies and animal models." CERCAT's research goals will be accomplished through three highly interactiveprojects: 1) "Metal chelators and thiols in endothelial function, and CVD" (Balz Frei); 2) "Lower vulnerability to toxins in aging by treatment with lipoic acid" (Tory Hagen); and 3) "CAM antioxidants and ALS" (Joseph Beckman). Center Investigators will be aided by an Administrative Core, which handles budgetary, reporting, and external advisory needs. In summary, CERCAT will investigate the efficacy of CAM antioxidants in ALS, CVD and aging, and provide the essential knowledge about the underlying mechanisms, dose-response effects, and relevant biological targets to advance these CAM therapies to human trials; equally important, the studies will test for untoward effects that might discourage CAM antioxidant therapies from proceeding to human studies.