Wilson病(WD)是可治性铜代谢障碍性遗传病，但许多难治性脑型WD患者驱铜疗效差，工作和生活能力严重受损。研究证实，铜代谢异常致细胞内铁稳态失衡是这些患者脑损伤的重要机制，铁依赖性ferroptosis与其损伤机制相契合，作为ferroptosis的重要调控通路，p62-Keap1-NRF2是潜在的治疗靶点。申请人团队根据WD中医辩证研究结果，创用通腑养髓方治疗脑型WD患者获得显效，并研究了通腑养髓方对神经元损伤的保护机制。基于此，本项目假设通腑养髓方通过调控p62-Keap1-NRF2通路阻断ferroptosis而具有神经元保护作用，分别抑制该通路的不同环节，研究通腑养髓方对WD模型TX小鼠神经元损伤的保护机制，明确其具体治疗靶点，从现代医学角度诠释通腑养髓方治疗脑型WD的疗效机制。本项目对提高脑型WD疗效、改善患者预后有重要意义，并为中医药防治其他神经遗传变性病提供新的治法思路。

Wilson disease (WD) is a treatable inherited disease characteristic by metabolic disorder of copper, however, many refractory WD patients with cerebral type acquired poor curative effects with decopper treatment and their working and living ability were badly damaged. Studies have confirmed that the unbalance of cellular iron homeostasis due to metabolic disorder of copper is an important mechanism for them and ferroptosis, an iron-dependent form of nonapoptotic cell death, was found to be in accord with the pathogenesis of neuron injury of WD. Because p62-Keap1-NRF2 is an important regulation pathway for ferroptosis, it is a potential therapeutic target for these patients.The applicant and his team members treated WD patients with cerebral type with Tongfu-Yangsui recipe on the basis of research results of the Syndrome Differentiation of TCM of WD and acquired perfect curative effects, the protection mechanisms of Tongfu-Yangsui recipe on neuron injury were studied subsequently. In this project, we assume that Tongfu-Yangsui recipe had the function of neuron protection which could block ferroptosis through p62-Keap1-NRF2 regulation pathways and carry out the following works: Study the protection mechanism of Tongfu-Yangsui recipe on neurons damage of TX mouse, a WD model, through inhibiting each steps of this pathway, ascertain concrete therapeutic targets of Tongfu-Yangsui recipe and explain the therapeutic mechanism of Tongfu-Yangsui recipe for WD patients with cerebral type from the perspective of modern medicine. Therefore, this project will have important implications for improving therapeutic effects and prognosis of WD patients with cerebral type and provide new therapeutic targets and the research ideas for the prevention and treatment of other nerve genetic degeneration diseases with traditional Chinese medicine.