Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regeneration
Several disease-modulatory FDA-approved drugs are being used in patients with neurodegenerative diseases. However, information on their toxicity-related profiles is very limited. Therefore, measurement of drug toxicity is essential to increase the knowledge of their side effects. This study aimed to...
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.984461/full |
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| author | Ankita Kumari Ankita Kumari Ankita Kumari Xin-An Zeng Xin-An Zeng Xin-An Zeng Abdul Rahaman Abdul Rahaman Abdul Rahaman Muhammad Adil Farooq Yanyan Huang Mahafooj Alee Runyu Yao Runyu Yao Murtaza Ali Murtaza Ali Murtaza Ali Ibrahim Khalifa Ibrahim Khalifa Omnia Badr Omnia Badr |
| author_facet | Ankita Kumari Ankita Kumari Ankita Kumari Xin-An Zeng Xin-An Zeng Xin-An Zeng Abdul Rahaman Abdul Rahaman Abdul Rahaman Muhammad Adil Farooq Yanyan Huang Mahafooj Alee Runyu Yao Runyu Yao Murtaza Ali Murtaza Ali Murtaza Ali Ibrahim Khalifa Ibrahim Khalifa Omnia Badr Omnia Badr |
| author_sort | Ankita Kumari |
| collection | DOAJ |
| description | Several disease-modulatory FDA-approved drugs are being used in patients with neurodegenerative diseases. However, information on their toxicity-related profiles is very limited. Therefore, measurement of drug toxicity is essential to increase the knowledge of their side effects. This study aimed to identify compounds that can modulate M-cell regeneration by causing neuro-protection and -toxicity. Here, we developed a simple and efficient in vivo assay using Tg (hsp: Gal4FF62A; UAS: nfsB-mCherry) transgenic zebrafish larvae. Interestingly, via the phenotype-based drug screening approach, we rapidly investigated 1,260 compounds from the United States drug collection and validated these in large numbers, including 14 compounds, that were obstructing this regeneration process. Next, 4 FDA-approved drugs out of 14 compounds were selected as the lead hits for in silico analysis to clarify their binding patterns with PTEN and SOCS3 signaling due to their significant potential in the inhibition of axon regeneration. Molecular docking studies indicated good binding affinity of all 4 drugs with the respective signaling molecules. This may point to PTEN and SOCS3 as the signaling molecules responsible for reducing axon regeneration. Moreover, the acute effect of compounds in reducing M-cell regeneration delineated their toxic effect. In conclusion, our in vivo along with in silico screening strategy will promote the rapid translation of new therapeutics to improve knowledge of the toxicity profile of approved/non-approved drugs efficiently. |
| first_indexed | 2024-04-10T23:03:44Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-10T23:03:44Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-acec8718223d4780988ef211a8b36e112023-01-13T16:04:50ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-10-01910.3389/fmolb.2022.984461984461Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regenerationAnkita Kumari0Ankita Kumari1Ankita Kumari2Xin-An Zeng3Xin-An Zeng4Xin-An Zeng5Abdul Rahaman6Abdul Rahaman7Abdul Rahaman8Muhammad Adil Farooq9Yanyan Huang10Mahafooj Alee11Runyu Yao12Runyu Yao13Murtaza Ali14Murtaza Ali15Murtaza Ali16Ibrahim Khalifa17Ibrahim Khalifa18Omnia Badr19Omnia Badr20School of Food Science and Engineering, South China University of Technology, Guangzhou, ChinaGuangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, Guangdong, ChinaOverseas Expertise Introduction Centre for Discipline Innovation of Food Nutrition and Human Health (111 Centre), Guangzhou, ChinaSchool of Food Science and Engineering, South China University of Technology, Guangzhou, ChinaGuangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, Guangdong, ChinaOverseas Expertise Introduction Centre for Discipline Innovation of Food Nutrition and Human Health (111 Centre), Guangzhou, ChinaSchool of Food Science and Engineering, South China University of Technology, Guangzhou, ChinaGuangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, Guangdong, ChinaOverseas Expertise Introduction Centre for Discipline Innovation of Food Nutrition and Human Health (111 Centre), Guangzhou, ChinaDepartment of Food Science and Technology, Khwaja Fareed University of Engineering and Information Technology, Rahimyar Khan, Punjab, PakistanGuangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, Guangdong, ChinaSchool of Food Science and Engineering, South China University of Technology, Guangzhou, ChinaSchool of Food Science and Engineering, South China University of Technology, Guangzhou, ChinaOverseas Expertise Introduction Centre for Discipline Innovation of Food Nutrition and Human Health (111 Centre), Guangzhou, ChinaSchool of Food Science and Engineering, South China University of Technology, Guangzhou, ChinaGuangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, Guangdong, ChinaOverseas Expertise Introduction Centre for Discipline Innovation of Food Nutrition and Human Health (111 Centre), Guangzhou, ChinaDepartment of Food Science and Technology, Khwaja Fareed University of Engineering and Information Technology, Rahimyar Khan, Punjab, PakistanFood Technology Department, Faculty of Agriculture, Benha University, Qalyubia, EgyptDepartment of Food Science and Technology, Khwaja Fareed University of Engineering and Information Technology, Rahimyar Khan, Punjab, PakistanDepartment of Genetics and Genetic Engineering, Faculty of Agriculture, Benha University, Qalyubia, EgyptSeveral disease-modulatory FDA-approved drugs are being used in patients with neurodegenerative diseases. However, information on their toxicity-related profiles is very limited. Therefore, measurement of drug toxicity is essential to increase the knowledge of their side effects. This study aimed to identify compounds that can modulate M-cell regeneration by causing neuro-protection and -toxicity. Here, we developed a simple and efficient in vivo assay using Tg (hsp: Gal4FF62A; UAS: nfsB-mCherry) transgenic zebrafish larvae. Interestingly, via the phenotype-based drug screening approach, we rapidly investigated 1,260 compounds from the United States drug collection and validated these in large numbers, including 14 compounds, that were obstructing this regeneration process. Next, 4 FDA-approved drugs out of 14 compounds were selected as the lead hits for in silico analysis to clarify their binding patterns with PTEN and SOCS3 signaling due to their significant potential in the inhibition of axon regeneration. Molecular docking studies indicated good binding affinity of all 4 drugs with the respective signaling molecules. This may point to PTEN and SOCS3 as the signaling molecules responsible for reducing axon regeneration. Moreover, the acute effect of compounds in reducing M-cell regeneration delineated their toxic effect. In conclusion, our in vivo along with in silico screening strategy will promote the rapid translation of new therapeutics to improve knowledge of the toxicity profile of approved/non-approved drugs efficiently.https://www.frontiersin.org/articles/10.3389/fmolb.2022.984461/fullphenotype drug screening (PDS)regenerationzebrafishaxonM-cell |
| spellingShingle | Ankita Kumari Ankita Kumari Ankita Kumari Xin-An Zeng Xin-An Zeng Xin-An Zeng Abdul Rahaman Abdul Rahaman Abdul Rahaman Muhammad Adil Farooq Yanyan Huang Mahafooj Alee Runyu Yao Runyu Yao Murtaza Ali Murtaza Ali Murtaza Ali Ibrahim Khalifa Ibrahim Khalifa Omnia Badr Omnia Badr Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regeneration Frontiers in Molecular Biosciences phenotype drug screening (PDS) regeneration zebrafish axon M-cell |
| title | Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regeneration |
| title_full | Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regeneration |
| title_fullStr | Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regeneration |
| title_full_unstemmed | Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regeneration |
| title_short | Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regeneration |
| title_sort | phenotype based drug screening an in vivo strategy to classify and identify the chemical compounds modulating zebrafish m cell regeneration |
| topic | phenotype drug screening (PDS) regeneration zebrafish axon M-cell |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.984461/full |
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