Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysis
Autism spectrum disorders (ASD) are a complex sequelae of neurodevelopmental disorders which manifest in the form of communication and social deficits. Currently, only two agents, namely risperidone and aripiprazole have been approved for the treatment of ASD, and there is a dearth of more drugs for...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | IBRO Neuroscience Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242123022534 |
| _version_ | 1797383641826852864 |
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| author | Ranjana Bhandari Manasi Varma Priyanka Rana Neelima Dhingra Anurag Kuhad |
| author_facet | Ranjana Bhandari Manasi Varma Priyanka Rana Neelima Dhingra Anurag Kuhad |
| author_sort | Ranjana Bhandari |
| collection | DOAJ |
| description | Autism spectrum disorders (ASD) are a complex sequelae of neurodevelopmental disorders which manifest in the form of communication and social deficits. Currently, only two agents, namely risperidone and aripiprazole have been approved for the treatment of ASD, and there is a dearth of more drugs for the disorder. The exact pathophysiology of autism is not understood clearly, but research has implicated multiple pathways at different points in the neuronal circuitry, suggesting their role in ASD. Among these, the role played by neuroinflammatory cascades like the NF-KB and Nrf2 pathways, and the excitotoxic glutamatergic system, are said to have a bearing on the development of ASD. Similarly, the GPR40 receptor, present in both the gut and the blood brain barrier, has also been said to be involved in the disorder. Consequently, molecules which can act by interacting with one or multiple of these targets might have a potential in the therapy of the disorder, and for this reason, this study was designed to assess the binding affinity of taurine, a naturally-occurring amino acid, with these target molecules. The same was scored against these targets using in-silico docking studies, with Risperidone and Aripiprazole being used as standard comparators. Encouraging docking scores were obtained for taurine across all the selected targets, indicating promising target interaction. But the affinity for targets actually varied in the order NRF-KEAP > NF-κB > NMDA > Calcium channel > GPR 40. Given the potential implication of these targets in the pathogenesis of ASD, the drug might show promising results in the therapy of the disorder if subjected to further evaluations. |
| first_indexed | 2024-03-08T21:24:00Z |
| format | Article |
| id | doaj.art-28eafacd5501452c9d44e7671bd18897 |
| institution | Directory Open Access Journal |
| issn | 2667-2421 |
| language | English |
| last_indexed | 2024-03-08T21:24:00Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj.art-28eafacd5501452c9d44e7671bd188972023-12-21T07:38:29ZengElsevierIBRO Neuroscience Reports2667-24212023-12-0115170177Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysisRanjana Bhandari0Manasi Varma1Priyanka Rana2Neelima Dhingra3Anurag Kuhad4Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014, India; Corresponding authors.Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014, India; Pharmaceutical Chemistry & CADD-Lab, University Institute of Pharmaceutical Sciences, UGC, Centre of Advanced Study, Panjab University, Chandigarh 160 014, IndiaPharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014, India; Pharmaceutical Chemistry & CADD-Lab, University Institute of Pharmaceutical Sciences, UGC, Centre of Advanced Study, Panjab University, Chandigarh 160 014, IndiaPharmaceutical Chemistry & CADD-Lab, University Institute of Pharmaceutical Sciences, UGC, Centre of Advanced Study, Panjab University, Chandigarh 160 014, India; Corresponding authors.Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014, India; Corresponding authors.Autism spectrum disorders (ASD) are a complex sequelae of neurodevelopmental disorders which manifest in the form of communication and social deficits. Currently, only two agents, namely risperidone and aripiprazole have been approved for the treatment of ASD, and there is a dearth of more drugs for the disorder. The exact pathophysiology of autism is not understood clearly, but research has implicated multiple pathways at different points in the neuronal circuitry, suggesting their role in ASD. Among these, the role played by neuroinflammatory cascades like the NF-KB and Nrf2 pathways, and the excitotoxic glutamatergic system, are said to have a bearing on the development of ASD. Similarly, the GPR40 receptor, present in both the gut and the blood brain barrier, has also been said to be involved in the disorder. Consequently, molecules which can act by interacting with one or multiple of these targets might have a potential in the therapy of the disorder, and for this reason, this study was designed to assess the binding affinity of taurine, a naturally-occurring amino acid, with these target molecules. The same was scored against these targets using in-silico docking studies, with Risperidone and Aripiprazole being used as standard comparators. Encouraging docking scores were obtained for taurine across all the selected targets, indicating promising target interaction. But the affinity for targets actually varied in the order NRF-KEAP > NF-κB > NMDA > Calcium channel > GPR 40. Given the potential implication of these targets in the pathogenesis of ASD, the drug might show promising results in the therapy of the disorder if subjected to further evaluations.http://www.sciencedirect.com/science/article/pii/S2667242123022534Autism spectrum disorderGlutamateCalcium-channelsNF-KBNrf2Taurine |
| spellingShingle | Ranjana Bhandari Manasi Varma Priyanka Rana Neelima Dhingra Anurag Kuhad Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysis IBRO Neuroscience Reports Autism spectrum disorder Glutamate Calcium-channels NF-KB Nrf2 Taurine |
| title | Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysis |
| title_full | Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysis |
| title_fullStr | Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysis |
| title_full_unstemmed | Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysis |
| title_short | Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysis |
| title_sort | taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder asd an in silico analysis |
| topic | Autism spectrum disorder Glutamate Calcium-channels NF-KB Nrf2 Taurine |
| url | http://www.sciencedirect.com/science/article/pii/S2667242123022534 |
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