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Ample\nevidence indicate that PD manifests as a result of impaired anti-oxidative machinery leading to\nneuronal death wherein Cullin-3 has ascended as a potential therapeutic target for diseases\ninvolving damaged anti-oxidative machinery.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective:<\/jats:title>\n<jats:p>The design of target specific inhibitors for the Cullin-3 protein might be a promising\nstrategy to increase the Nrf2 levels and to decrease the possibility of \u201coff-target\u201d toxic properties.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>In the present study, an integrated computational and wet lab approach was adopted to\nidentify small molecule inhibitors for Cullin-3. The rational drug designing process comprised\nhomology modeling and derivation of the pharmacophore for Cullin-3, virtual screening of Zinc\nnatural compound database, molecular docking and Molecular dynamics based screening of ligand\nmolecules. In vivo validations of an identified lead compound were conducted in the PD model of\nC. elegans.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results and Discussion:<\/jats:title>\n<jats:p>Our strategy yielded a potential inhibitor; (Glide score = -12.31), which\nwas evaluated for its neuroprotective efficacy in the PD model of C. elegans. The inhibitor was able\nto efficiently defend against neuronal death in PD model of C. elegans and the neuroprotective effects\nwere attributed to its anti-oxidant activities, supported by the increase in superoxide dismutase,\ncatalase and the diminution of acetylcholinesterase and reactive oxygen species levels. In addition, the\nCullin-3 inhibitor significantly restored the behavioral deficits in the transgenic C. elegans.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>Taken together, these findings highlight the potential utility of Cullin-3 inhibition to\nblock the persistent neuronal death in PD. Further studies focusing on Cullin-3 and its mechanism\nof action would be interesting.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1386207323666200514074128","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T16:43:21Z","timestamp":1589474601000},"page":"814-826","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In silico and In vivo Evaluation of Oxidative Stress Inhibitors Against Parkinson's Disease using the C. elegans Model"],"prefix":"10.2174","volume":"23","author":[{"given":"Pradeep","family":"Hanumanthappa","sequence":"first","affiliation":[{"name":"Department of Studies in Biotechnology, University of Mysore, Manasagangothri, Mysore 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpitha","family":"Ashok","sequence":"additional","affiliation":[{"name":"Department of Studies in Biotechnology, University of Mysore, Manasagangothri, Mysore 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inderjit","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Studies in Biotechnology, University of Mysore, Manasagangothri, Mysore 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmel I.","family":"Priya","sequence":"additional","affiliation":[{"name":"Department of Studies in Biotechnology, University of Mysore, Manasagangothri, Mysore 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Zinzala","sequence":"additional","affiliation":[{"name":"Department of Studies in Biotechnology, University of Mysore, Manasagangothri, Mysore 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya V.","family":"Marigowda","sequence":"additional","affiliation":[{"name":"Department of Studies in Biotechnology, University of Mysore, Manasagangothri, Mysore 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna H.","family":"Sosalegowda","sequence":"additional","affiliation":[{"name":"Department of Studies in Biotechnology, University of Mysore, Manasagangothri, Mysore 570 006, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s12041-018-0960-6","volume":"97","author":"Ghatak S.","year":"2018","unstructured":"Ghatak S.; Trudler D.; Dolatabadi N.; Ambasudhan R.; Parkinson\u2019s disease: what the model systems have taught us so far. 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