Gene expression data from HD mutant and wild type ST14A cells, differentiated for 24 hours and treated with vehicle (DMSO) or with 5µM MIND4

MIND4 treatment significantly reduced levels of TNF-alpha in the cortex of symptomatic HD mice, demonstrating the neuroprotective anti-inflammatory potential of NRF2 activator in the CNS. A high affinity reversible binding of MIND4 ligands to the NRF2 inhibitor, KEAP1, was identified by a docking model and confirmed by mechanistic studies, suggesting a novel approach to activating the NRF2 pathway. The results offer a new therapeutic path for HD and other human diseases.MIND4可显著降低症状性亨廷顿舞蹈病（Huntington's Disease, HD）小鼠大脑皮层中的肿瘤坏死因子-α（TNF-alpha）水平，证实了核因子E2相关因子2（NRF2）激活剂在中枢神经系统（Central Nervous System, CNS）中的神经保护抗炎潜能。研究通过分子对接模型鉴定出MIND4配体与NRF2抑制剂KEAP1具有高亲和力可逆结合特性，并经机制研究验证，这提示了一条激活NRF2通路的全新策略。该研究结果为HD及其他人类疾病提供了全新的治疗途径。