当前位置: X-MOL 学术Adv. Therap. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Mitochondrial-Targeting Vitamin B3 Ameliorates the Phenotypes of Parkinson's Disease In Vitro and In Vivo by Restoring Mitochondrial Function
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2022-08-31 , DOI: 10.1002/adtp.202200094
Chenqi Xin 1, 2 , Naidi Yang 1 , Yaqi Ding 1 , Linqi Han 1 , Zhiqiang Zhou 1 , Xiaolu Guo 1 , Zhijie Fang 1 , Hua Bai 3 , Bo Peng 3 , Chengwu Zhang 4 , Lin Li 1, 3, 5
Affiliation  

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by progressive dopaminergic neuron loss, which affects millions of people worldwide, especially elderly individuals. Mitochondrial dysfunction is believed to be one crucial causative factor of PD. Therefore, restoring mitochondrial function is highly recommended for the treatment of PD. Herein, it is found that vitamin B3 (VB3) protects the dopaminergic cell line SH-SY5Y against rotenone-induced apoptosis by restoring mitochondrial dysfunction. To further improve the efficacy, a derivative of VB3, mitochondrial-targeting VB3 (Mito-VB3), is developed. It is demonstrated that Mito-VB3 rescues SH-SY5Y cells from the neurotoxicity of oxidative stress. More importantly, Mito-VB3 ameliorates the phenotypes of the Drosophila PD model. Mechanistically, Mito-VB3 enhances nicotinamide adenine dinucleotide (NAD+) levels, reduces ROS generation, elevates ATP levels, and restores mitochondrial membrane potential. Meanwhile, Mito-VB3 promotes mitochondrial biogenesis by activating the NAD+/SIRT1/PGC1α pathway. In summary, the results demonstrate that Mito-VB3 displays remarkable neuroprotective effects in the cell and Drosophila PD models and that Mito-VB3 might serve as a potential therapeutic candidate for the treatment of PD and other mitochondrial dysfunction-related diseases.

中文翻译:

线粒体靶向维生素 B3 通过恢复线粒体功能在体外和体内改善帕金森病的表型

帕金森病 (PD) 是第二种最常见的神经退行性疾病,其特征是进行性多巴胺能神经元丢失,影响全世界数百万人,尤其是老年人。线粒体功能障碍被认为是 PD 的一个重要致病因素。因此,强烈推荐恢复线粒体功能来治疗 PD。在此,发现维生素 B 3 (VB 3 ) 通过恢复线粒体功能障碍保护多巴胺能细胞系 SH-SY5Y 免受鱼藤酮诱导的细胞凋亡。为了进一步提高疗效,开发了VB 3的衍生物,线粒体靶向VB 3 (Mito-VB 3 )。结果表明,Mito-VB 3从氧化应激的神经毒性中拯救 SH-SY5Y 细胞。更重要的是,Mito-VB 3改善了果蝇PD 模型的表型。从机制上讲,Mito-VB 3可提高烟酰胺腺嘌呤二核苷酸 (NAD + ) 水平、减少 ROS 生成、提高 ATP 水平并恢复线粒体膜电位。同时,Mito-VB 3通过激活 NAD + /SIRT1/PGC1α 通路促进线粒体生物发生。总之,结果表明 Mito-VB 3在细胞和果蝇PD 模型中显示出显着的神经保护作用,并且 Mito-VB 3可能作为治疗 PD 和其他线粒体功能障碍相关疾病的潜在治疗候选物。
更新日期:2022-08-31
down
wechat
bug