CAM Antioxidants and ALS

在过去的十年里，ALS患者的生活质量从更好的营养， 呼吸支持和各种补充和替代药物（CAM）。ALS患者的CAM 被传统医学界广泛接受。我们的长期目标是找到 治疗行动，以减缓运动神经元的进行性死亡，定义ALS，把这种致命的 将疾病转化为类似于脊髓灰质炎后综合征的慢性疾病。一个重要的线索来自于 抗氧化剂铜、锌超氧化物歧化酶的突变导致2-3%的ALS患者。我们发现 突变有利于SOD中锌的丢失，通过增加硝化作用对运动神经元有毒， 提示锌营养状况可能将2%的家族性SOD患者与其余98%的ALS患者联系起来 患者我们的研究还表明，运动神经元周围星形胶质细胞的硝化应激 导致运动神经元的逐渐死亡ALS突变SOD在转基因小鼠中的表达 大鼠现在被广泛用于研究传统疗法和CAM疗法对生存的影响。与 为了更好地了解SOD如何发生故障导致ALS，我们已经确定了几种新的CAM 抗氧化剂治疗可以调节ALS的进展。使用细胞培养和 通过对转基因大鼠脊髓的微量分析方法，我们将表征CAM疗法的能力， 来调节这些动物的疾病进展。我们的第一个目标是确定锌是否可以减缓 转基因SOD大鼠中ALS的进展以及重金属螯合治疗是否无意中 通过去除锌来加速ALS。我们的第二个目标是确定是否由 锌缺乏的SOD使脊髓易受α-生育酚缺乏的影响。我们的最终目标是 表征硫辛酸是否可以改善α-生育酚缺乏症的影响或降低其毒性， SOD对衰老大鼠的影响我们提出的研究将提供一个机制的基础，研究如何CAM 抗氧化剂疗法可以被协调以调节ALS的进程。

The quality of life of ALS patients has substantially improved in the past decade from better nutrition, respiratory support and a variety of complementary and alternative medicines (CAM). CAM for ALS patients is well accepted by the traditional medical community. Our long-term goal is to find a combination of therapeutic actions to slow the progressive death of motor neurons that defines ALS, turning this fatal disease into a chronic condition resembling post-polio syndrome. An important clue came from discovering mutations to the antioxidant copper, zinc superoxide dismutase cause 2-3% of ALS patients. We found that the loss of zinc from SOD, which is favored by the mutations, is toxic to motor neurons by increasing nitrative stress, suggesting zinc status could link the 2% familial SOD patients with the remaining 98% of ALS patients. Our research has also shown that nitrative stress in astrocytes surrounding motor neurons contributes to the progressive death of motor neurons. Expression of ALS-mutant SODs in transgenic mice and rats is now widely used to study the effects of both traditional as well as CAM therapies on survival. With a better understanding of how SOD malfunctions to cause ALS, we have identified several novel CAM antioxidant therapies that could modulate the progression of ALS. Using a combination of cell culture and microanalytical methods of spinal cord from transgenic rats, we will characterize the ability of CAM therapies to modulate disease progression in these animals. Our first aim is to determine whether zinc can slow the progression of ALS in transgenic SOD rats and whether heavy metal chelation therapy unintentionally may accelerate ALS by removing zinc. Our second aim will characterize whether the depletion of ascorbate by zinc deficient SOD makes the spinal cord vulnerable to a-tocopherol deficiencies. Our final aim will characterize whether lipoic acid can ameliorate the effects of a-tocopherol deficiency or reduce the toxic effects of SOD in aging rats. Our proposed studies will provide a mechanistic basis for examining how CAM antioxidant therapies can be coordinated to modulate the course of ALS.