Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2  

作　　者：Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang 

机构地区：[1]Department of Physiology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Jinan,Shandong Province,China [2]Department of Medical Psychology and Ethics,School of Basic Medicine Sciences,Cheeloo College of Medicine,Shandong University,Jinan,Shandong Province,China [3]Department of Neurosurgery Surgery,Qingdao Municipal Hospital,Qingdao,Shandong Province,China

出　　处：《Neural Regeneration Research》2025年第6期1776-1788,共13页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。

摘　　要：The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关 键 词：apoptosis CYSTATHIONINE-Β-SYNTHASE nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide MITOCHONDRION NEUROPLASTICITY oxidative stress quinolinic acid reactive oxygen species 

分 类 号：R742.2[医药卫生—神经病学与精神病学]