title: Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington's disease.
abstract: 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.
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh, 160014, India, sandhir@pu.ac.in.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
authors.forename: Aarti
authors.initials: A
authors.lastname: Yadav
authors.forename: Arpit
authors.initials: A
authors.lastname: Mehrotra
authors.forename: Aditya
authors.initials: A
authors.lastname: Sunkaria
authors.forename: Amandeep
authors.initials: A
authors.lastname: Singh
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001259:Ataxia / Q000188:drug therapy / Q000209:etiology; D003342:Corpus Striatum / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D007794:Lameness, Animal / Q000139:chemically induced / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics; D053758:Nanoparticles; D009574:Nitro Compounds / Q000633:toxicity; D018384:Oxidative Stress; D008517:Phytotherapy; D011422:Propionates / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D009574:Nitro Compounds; D011422:Propionates; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D005978:Glutathione; D003474:Curcumin; C015392:3-nitropropionic acid