Mitochondrial Metabolites to Treat Parkinson's Disease

由于氧化引起的线粒体衰退是帕金森病（PD）和其他衰老性神经退行性疾病的重要原因。我们以前已经表明，老年大鼠的线粒体衰退可以通过喂食正常的线粒体代谢物R-α-硫辛酸（LA）和乙酰-L-肉碱（ALCAR）来改善，这抑制了氧化损伤并恢复了老年动物的大部分线粒体结构和功能。有证据表明，一些线粒体代谢物可以防止PD。例如，辅酶Q10（CoQ）已被证明可以在人类临床试验中保护PD; ALCAR已被证明可以保护1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的毒性，这是猴子中的PD模拟物。这些代谢物通过恢复线粒体抗氧化剂和功能来保护。我们假设，线粒体抗氧化剂/代谢物CoQ、ALCAR和LA的混合物可以被优化，以比任何单一化合物在预防或治疗PD方面更有效。我们将测试我们的假设，使用行为，生化和免疫组化技术的两个模型的PD：慢性鱼藤酮暴露的SK-N-MC人神经母细胞瘤细胞模型和慢性鱼藤酮治疗的大鼠模型。这个PD项目是我们预防线粒体衰变工作的一个新方向，可能会导致PD的有效和成本效益的预防/治疗。

Mitochondrial decay due to oxidation is an important contributor to Parkinson's disease (PD) and other neurodegenerative diseases of aging. We have previously shown that mitochondrial decay in old rats can be ameliorated by feeding them the normal mitochondrial metabolites R-alpha-lipoic acid (LA) and acetyl-L-carnitine (ALCAR), which inhibited oxidative damage and restored much of the mitochondrial structure and function in old animals. There is evidence that some mitochondrial metabolites may protect against PD. For example, coenzyme Q10 (CoQ) has been shown to protect against PD in clinical trials in humans; and ALCAR has been shown to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity, a PD mimic in monkeys. These metabolites protect by restoring mitochondrial antioxidants and function. We hypothesize that a mixture of mitochondrial antioxidants/metabolites, CoQ, ALCAR and LA, could be optimized to be more effective than any single compound in preventing or treating PD. We will test our hypothesis using behavioral, biochemical, and immunohistochemical techniques on two models of PD: the chronic rotenone-exposed SK-N-MC human neuroblastoma cell model and the chronic rotenone-treated rat model. This project on PD is a new direction for our work on preventing mitochondrial decay and could lead to an effective and cost efficient prevention /therapy for PD.