Structure based molecular inhibition of Caspase-8 for treatment of multi-neurodegenerative diseases using known
Khurshid Ahmad1, Saif Khan2, Mohd Adil3
1Department of Biosciences, Integral University, Lucknow.
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.
Insights
Natural compounds rosmarinic acid and curcumin show potential for inhibiting Caspase-8, a key factor in neurodegenerative diseases like Alzheimer's and Parkinson's. Further research is needed to confirm their therapeutic benefits.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Neurodegenerative disorders are characterized by excessive neuronal apoptosis.
- Caspase-8, an initiator caspase, is a critical mediator of neuronal apoptosis and implicated in diseases like Alzheimer's, Parkinson's, and Huntington's.
- Inhibiting Caspase-8 presents a potential therapeutic strategy for neurodegenerative conditions.
Purpose of the Study:
- To investigate the molecular interactions of selected natural compounds with anti-neurodegenerative properties against Caspase-8.
- To identify potent natural inhibitors of Caspase-8 for potential therapeutic applications.
Main Methods:
- Molecular docking simulations were performed using Autodock4.2.
- The study focused on the binding interactions between Caspase-8 and selected natural compounds.
- Binding energy (ΔG) was calculated to assess inhibitory potential.
Main Results:
- Rosmarinic acid exhibited a binding energy of -7.10 Kcal/mol with Caspase-8.
- Curcumin demonstrated a binding energy of -7.08 Kcal/mol with Caspase-8.
- Both rosmarinic acid and curcumin were identified as potent inhibitors of Caspase-8.
Conclusions:
- Rosmarinic acid and curcumin show significant potential as Caspase-8 inhibitors.
- These compounds may offer a novel therapeutic avenue for neurodegenerative disorders.
- Further in vitro and in vivo studies are required to validate their anti-neurodegenerative efficacy.
