title: Implication of Caspase-3 as a Common Therapeutic Target for Multineurodegenerative Disorders and Its Inhibition Using Nonpeptidyl Natural Compounds.
abstract: Caspase-3 has been identified as a key mediator of neuronal apoptosis. The present study identifies caspase-3 as a common player involved in the regulation of multineurodegenerative disorders, namely, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The protein interaction network prepared using STRING database provides a strong evidence of caspase-3 interactions with the metabolic cascade of the said multineurodegenerative disorders, thus characterizing it as a potential therapeutic target for multiple neurodegenerative disorders. In silico molecular docking of selected nonpeptidyl natural compounds against caspase-3 exposed potent leads against this common therapeutic target. Rosmarinic acid and curcumin proved to be the most promising ligands (leads) mimicking the inhibitory action of peptidyl inhibitors with the highest Gold fitness scores 57.38 and 53.51, respectively. These results were in close agreement with the fitness score predicted using X-score, a consensus based scoring function to calculate the binding affinity. Nonpeptidyl inhibitors of caspase-3 identified in the present study expeditiously mimic the inhibitory action of the previously identified peptidyl inhibitors. Since, nonpeptidyl inhibitors are preferred drug candidates, hence, discovery of natural compounds as nonpeptidyl inhibitors is a significant transition towards feasible drug development for neurodegenerative disorders.
authors.affiliation: Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha'il, Ha'il 2440, Saudi Arabia.
authors.forename: Saif
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Biosciences, Integral University, Lucknow, Uttar Pradesh 226026, India.
authors.forename: Khurshid
authors.initials: K
authors.lastname: Ahmad
authors.affiliation: Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha'il, Ha'il 2440, Saudi Arabia.
authors.forename: Eyad M A
authors.initials: EM
authors.lastname: Alshammari
authors.affiliation: Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha'il, Ha'il 2440, Saudi Arabia.
authors.forename: Mohd
authors.initials: M
authors.lastname: Adnan
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan 712749, Republic of Korea.
authors.forename: Mohd Hassan
authors.initials: MH
authors.lastname: Baig
authors.affiliation: Department of Biosciences, Integral University, Lucknow, Uttar Pradesh 226026, India.
authors.forename: Mohtashim
authors.initials: M
authors.lastname: Lohani
authors.affiliation: Department of Biotechnology, TERI University, New Delhi 110070, India.
authors.forename: Pallavi
authors.identifier: 0000-0003-1214-9374
authors.initials: P
authors.lastname: Somvanshi
authors.affiliation: Research and Scientific Studies Unit, College of Nursing & Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia ; Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
authors.forename: Shafiul
authors.initials: S
authors.lastname: Haque
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000737:chemistry*; D061945:Caspase Inhibitors / Q000737:chemistry*; D002934:Cinnamates / Q000737:chemistry* / Q000627:therapeutic use; D003474:Curcumin / Q000737:chemistry* / Q000627:therapeutic use; D053630:Depsides / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000473:pathology; D008024:Ligands; D062105:Molecular Docking Simulation; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology; D000097123:Rosmarinic Acid
chemical_list: D053148:Caspase 3; D061945:Caspase Inhibitors; D002934:Cinnamates; D003474:Curcumin; D053630:Depsides; D008024:Ligands; D000097123:Rosmarinic Acid