The Mental Health Research Institute, the University of Melbourne, Victoria 3010 Australia.
J Exp Med. 2012 Apr 9;209(4):837-54. doi: 10.1084/jem.20112285. Epub 2012 Apr 2.
Parkinson's disease (PD) is a progressive, chronic disease characterized by dyskinesia, rigidity, instability, and tremors. The disease is defined by the presence of Lewy bodies, which primarily consist of aggregated α-synuclein protein, and is accompanied by the loss of monoaminergic neurons. Current therapeutic strategies only give symptomatic relief of motor impairment and do not address the underlying neurodegeneration. Hence, we have identified Cu(II)(atsm) as a potential therapeutic for PD. Drug administration to four different animal models of PD resulted in improved motor and cognition function, rescued nigral cell loss, and improved dopamine metabolism. In vitro, this compound is able to inhibit the effects of peroxynitrite-driven toxicity, including the formation of nitrated α-synuclein oligomers. Our results show that Cu(II)(atsm) is effective in reversing parkinsonian defects in animal models and has the potential to be a successful treatment of PD.
帕金森病(PD)是一种进行性、慢性疾病,其特征为运动障碍、僵硬、不稳定和震颤。该疾病由路易体的存在定义,路易体主要由聚集的α-突触核蛋白组成,并伴有单胺能神经元的丧失。目前的治疗策略仅能缓解运动障碍的症状,而不能解决潜在的神经退行性变。因此,我们已经确定 Cu(II)(atsm) 是 PD 的一种潜在治疗药物。该药物对四种不同的 PD 动物模型进行给药,结果显示运动和认知功能得到改善,黑质细胞损失得到挽救,多巴胺代谢得到改善。在体外,该化合物能够抑制过氧亚硝酸盐驱动的毒性的影响,包括硝化α-突触核蛋白寡聚物的形成。我们的研究结果表明,Cu(II)(atsm) 能够有效逆转动物模型中的帕金森缺陷,并有潜力成为 PD 的成功治疗方法。