Sandhir Rajat, Yadav Aarti, Mehrotra Arpit, Sunkaria Aditya, Singh Amandeep, Sharma Sadhna
Department of Biochemistry, Panjab University, Chandigarh, 160014, India,
Neuromolecular Med. 2014 Mar;16(1):106-18. doi: 10.1007/s12017-013-8261-y. Epub 2013 Sep 6.
Till date, an exact causative pathway responsible for neurodegeneration in Huntington's disease (HD) remains elusive; however, mitochondrial dysfunction appears to play an important role in HD pathogenesis. Therefore, strategies to attenuate mitochondrial impairments could provide a potential therapeutic intervention. In the present study, we used curcumin encapsulated solid lipid nanoparticles (C-SLNs) to ameliorate 3-nitropropionic acid (3-NP)-induced HD in rats. Results of MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and succinate dehydrogenase (SDH) staining of striatum revealed a marked decrease in Complex II activity. However, C-SLN-treated animals showed significant increase in the activity of mitochondrial complexes and cytochrome levels. C-SLNs also restored the glutathione levels and superoxide dismutase activity. Moreover, significant reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species was observed in rats treated with C-SLNs. Quantitative PCR and Western blot results revealed the activation of nuclear factor-erythroid 2 antioxidant pathway after C-SLNs administration in 3-NP-treated animals. In addition, C-SLN-treated rats showed significant improvement in neuromotor coordination when compared with 3-NP-treated rats. Thus, the results of this study suggest that C-SLNs administration might be a promising therapeutic intervention to ameliorate mitochondrial dysfunctions in HD.
迄今为止,亨廷顿舞蹈病(HD)中导致神经退行性变的确切致病途径仍不清楚;然而,线粒体功能障碍似乎在HD发病机制中起重要作用。因此,减轻线粒体损伤的策略可能提供一种潜在的治疗干预措施。在本研究中,我们使用姜黄素包裹的固体脂质纳米粒(C-SLNs)来改善3-硝基丙酸(3-NP)诱导的大鼠HD。MTT(3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐)检测结果和纹状体琥珀酸脱氢酶(SDH)染色显示复合物II活性显著降低。然而,C-SLN处理的动物线粒体复合物活性和细胞色素水平显著增加。C-SLNs还恢复了谷胱甘肽水平和超氧化物歧化酶活性。此外,在C-SLNs处理的大鼠中观察到线粒体肿胀、脂质过氧化、蛋白质羰基化和活性氧显著减少。定量PCR和蛋白质印迹结果显示,在3-NP处理的动物中给予C-SLNs后,核因子红细胞2相关因子2抗氧化途径被激活。此外,与3-NP处理的大鼠相比,C-SLN处理的大鼠神经运动协调能力有显著改善。因此,本研究结果表明,给予C-SLNs可能是改善HD中线粒体功能障碍的一种有前景的治疗干预措施。