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BioMed Research International
Volume 2015, Article ID 379817, 9 pages
http://dx.doi.org/10.1155/2015/379817
Research Article

Implication of Caspase-3 as a Common Therapeutic Target for Multineurodegenerative Disorders and Its Inhibition Using Nonpeptidyl Natural Compounds

1Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha’il, Ha’il 2440, Saudi Arabia
2Department of Biosciences, Integral University, Lucknow, Uttar Pradesh 226026, India
3School of Biotechnology, Yeungnam University, Gyeongsan 712749, Republic of Korea
4Department of Biotechnology, TERI University, New Delhi 110070, India
5Research and Scientific Studies Unit, College of Nursing & Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia
6Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India

Received 4 March 2015; Revised 13 April 2015; Accepted 14 April 2015

Academic Editor: Yudong Cai

Copyright © 2015 Saif Khan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.