Structure based molecular inhibition of Caspase-8 for treatment of multi-neurodegenerative diseases using known natural compounds |
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Authors: | Khurshid Ahmad Saif Khan Mohd Adil Mohd Saeed Ashwini Kumar Srivastava |
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Institution: | 1.Department of Biosciences, Integral University, Lucknow;2.College of Applied Medical Sciences, University of Ha׳il, Kingdom of Saudi Arabia;3.Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India |
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Abstract: | Neurodegenerative disorders are often associated with excessive neuronal apoptosis. It is well known that apoptosis is regulated
by some intracellular proteases, such as, Caspases (cysteine-dependent, aspartate-specific proteases). In fact, Caspase-8 which is an
initiator caspase, has been identified as a key mediator of neuronal apoptosis. In addition, Caspase-8 is found to be coupled with
the regulation of various neurodegenerative disorders including Alzheimer׳s disease (AD), Parkinson׳s disease (PD), Huntington׳s
Diseases (HD) and Dentatorubral Pallidoluysian Atrophy (DRPLA). Caspase-8 inhibition may provide an effective means of
treatment for multiple neurodegenerative disorders. Therefore, the present study describes the molecular interaction of some
selected natural compounds with known anti neurodegenerative properties with Caspase-8. Docking between Caspase-8 and each
of these compounds (separately) was performed using ‘Autodock4.2’. Out of all the selected compounds, rosmarinic acid and
curcumin proved to be the most potent inhibitors of Caspase-8 with binding energy (ΔG) of -7.10 Kcal/mol and -7.08 Kcal/mol,
respectively. However, further in vitro and in vivo studies are needed to validate the anti-neurodegenerative potential of these
compounds. |
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Keywords: | Neurodegenerative disorders Caspase 8 Natural compounds Molecular Docking |
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