Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis.
Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis.
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在肌萎缩侧索硬化症突变型 SOD1 细胞和小鼠模型中，和厚朴酚通过减少氧化应激和改善线粒体功能来减轻神经退行性变。
DOI：
10.1016/j.apsb.2022.07.019
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发表时间：
2023-02
影响因子：
14.5
通讯作者：
Peng, Ying
中科院分区：
文献类型：
--
作者：
Zhou, Yujun;Tang, Jingshu;Lan, Jiaqi;Zhang, Yong;Wang, Hongyue;Chen, Qiuyu;Kang, Yuying;Sun, Yang;Feng, Xinhong;Wu, Lei;Jin, Hongtao;Chen, Shizhong;Peng, Ying
关键词：
肌萎缩侧索硬化症（ALS）是一种影响上下运动神经元（MN）的进行性神经退行性疾病，具有大量未满足的医疗需求。多种病理机制被认为有助于ALS的进展，包括神经元氧化应激和线粒体功能障碍。和诺酮（HNK）已被报道在几种神经系统疾病模型中发挥治疗作用，包括缺血性中风、阿尔茨海默病和帕金森病。在这里，我们发现和厚朴在体外和体内ALS疾病模型中也表现出保护作用。和厚朴提高了表达突变型G93 A SOD 1蛋白的NSC-34运动神经元样细胞（简称SOD 1-G93 A细胞）的活力。机制研究表明，和厚朴通过增强谷胱甘肽（GSH）的合成和激活核因子红细胞2相关因子2（NRF 2）-抗氧化反应元件（ARE）途径减轻细胞氧化应激。此外，和厚朴通过微调SOD 1-G93 A细胞中的线粒体动力学来改善线粒体功能和形态。重要的是，和诺明延长了SOD 1-G93 A转基因小鼠的寿命，并改善了运动功能。在小鼠脊髓和腓肠肌中进一步证实了抗氧化能力和线粒体功能的改善。总的来说，和诺克林显示出作为ALS治疗的多靶点药物的有希望的临床前潜力。和厚朴酚通过激活NRF 2-GSH通路减轻氧化损伤。同时，和厚朴还通过调节线粒体生物合成和线粒体融合来改善线粒体功能障碍。总之，和诺啡肽在ALS模型中发挥神经保护作用。
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment. Honokiol decreased the oxidative damage by activating NRF2–GSH pathway. Meanwhile, honokiol improved mitochondrial dysfunction via regulating the mitochondrial biogenesis and mitochondrial fusion. Taken together, honokiol exerted neuroprotection in ALS models.
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DOI：
10.3390/antiox6020025
发表时间：
2017-04-05
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Gao J;Wang L;Liu J;Xie F;Su B;Wang X
通讯作者：
Wang X
DOI：
10.1111/j.1742-7843.2007.00082.x
发表时间：
2007-08-01
影响因子：
3.1
作者：
Chen, Chang-Mu;Liu, Shing-Hwa;Lin-Shiau, Shoei-Yn
通讯作者：
Lin-Shiau, Shoei-Yn
影响因子：
8
作者：
Hsiao, Yai-Ping;Chen, Hui-Ting;Jan, Tong-Rong
通讯作者：
Jan, Tong-Rong
影响因子：
4.4
作者：
Garcia I;Calderon F;la Torre P;Vallier SS;Rodriguez C;Agarwala D;Keniry M;Innis-Whitehouse W;Gilkerson R
通讯作者：
Gilkerson R
影响因子：
29
作者：
Herkenne, Stephanie;Ek, Olivier;Scorrano, Luca
通讯作者：
Scorrano, Luca