Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases
Autophagy is an intracellular degradation pathway for malfunctioning aggregation-prone proteins, damaged organelles, unwanted macromolecules and invading pathogens. This process is essential for maintaining cellular and tissue homeostasis that contribute to organismal survival. Autophagy dysfunction...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00038/full |
| _version_ | 1818060719032107008 |
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| author | Prashanta Kumar Panda Alexandra Fahrner Somya Vats Somya Vats Elena Seranova Vartika Sharma Miruna Chipara Priyal Desai Jorge Torresi Jorge Torresi Tatiana Rosenstock Tatiana Rosenstock Dhiraj Kumar Sovan Sarkar |
| author_facet | Prashanta Kumar Panda Alexandra Fahrner Somya Vats Somya Vats Elena Seranova Vartika Sharma Miruna Chipara Priyal Desai Jorge Torresi Jorge Torresi Tatiana Rosenstock Tatiana Rosenstock Dhiraj Kumar Sovan Sarkar |
| author_sort | Prashanta Kumar Panda |
| collection | DOAJ |
| description | Autophagy is an intracellular degradation pathway for malfunctioning aggregation-prone proteins, damaged organelles, unwanted macromolecules and invading pathogens. This process is essential for maintaining cellular and tissue homeostasis that contribute to organismal survival. Autophagy dysfunction has been implicated in the pathogenesis of diverse human diseases, and therefore, therapeutic exploitation of autophagy is of potential biomedical relevance. A number of chemical screening approaches have been established for the drug discovery of autophagy modulators based on the perturbations of autophagy reporters or the clearance of autophagy substrates. These readouts can be detected by fluorescence and high-content microscopy, flow cytometry, microplate reader and immunoblotting, and the assays have evolved to enable high-throughput screening and measurement of autophagic flux. Several pharmacological modulators of autophagy have been identified that act either via the classical mechanistic target of rapamycin (mTOR) pathway or independently of mTOR. Many of these autophagy modulators have been demonstrated to exert beneficial effects in transgenic models of neurodegenerative disorders, cancer, infectious diseases, liver diseases, myopathies as well as in lifespan extension. This review describes the commonly used chemical screening approaches in mammalian cells and the key autophagy modulators identified through these methods, and highlights the therapeutic benefits of these compounds in specific disease contexts. |
| first_indexed | 2024-12-10T13:36:53Z |
| format | Article |
| id | doaj.art-2fa86eda4901481e8895cb69bf3d562b |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-10T13:36:53Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-2fa86eda4901481e8895cb69bf3d562b2022-12-22T01:46:47ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-03-01710.3389/fcell.2019.00038442492Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human DiseasesPrashanta Kumar Panda0Alexandra Fahrner1Somya Vats2Somya Vats3Elena Seranova4Vartika Sharma5Miruna Chipara6Priyal Desai7Jorge Torresi8Jorge Torresi9Tatiana Rosenstock10Tatiana Rosenstock11Dhiraj Kumar12Sovan Sarkar13Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, IndiaInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomCellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomDepartment of Physiological Science, Santa Casa de São Paulo School of Medical Sciences, São Paulo, BrazilInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomDepartment of Physiological Science, Santa Casa de São Paulo School of Medical Sciences, São Paulo, BrazilCellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomAutophagy is an intracellular degradation pathway for malfunctioning aggregation-prone proteins, damaged organelles, unwanted macromolecules and invading pathogens. This process is essential for maintaining cellular and tissue homeostasis that contribute to organismal survival. Autophagy dysfunction has been implicated in the pathogenesis of diverse human diseases, and therefore, therapeutic exploitation of autophagy is of potential biomedical relevance. A number of chemical screening approaches have been established for the drug discovery of autophagy modulators based on the perturbations of autophagy reporters or the clearance of autophagy substrates. These readouts can be detected by fluorescence and high-content microscopy, flow cytometry, microplate reader and immunoblotting, and the assays have evolved to enable high-throughput screening and measurement of autophagic flux. Several pharmacological modulators of autophagy have been identified that act either via the classical mechanistic target of rapamycin (mTOR) pathway or independently of mTOR. Many of these autophagy modulators have been demonstrated to exert beneficial effects in transgenic models of neurodegenerative disorders, cancer, infectious diseases, liver diseases, myopathies as well as in lifespan extension. This review describes the commonly used chemical screening approaches in mammalian cells and the key autophagy modulators identified through these methods, and highlights the therapeutic benefits of these compounds in specific disease contexts.https://www.frontiersin.org/article/10.3389/fcell.2019.00038/fullautophagyautophagy reporterautophagy substrateautophagy modulatorscreening methodneurodegenerative diseases |
| spellingShingle | Prashanta Kumar Panda Alexandra Fahrner Somya Vats Somya Vats Elena Seranova Vartika Sharma Miruna Chipara Priyal Desai Jorge Torresi Jorge Torresi Tatiana Rosenstock Tatiana Rosenstock Dhiraj Kumar Sovan Sarkar Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases Frontiers in Cell and Developmental Biology autophagy autophagy reporter autophagy substrate autophagy modulator screening method neurodegenerative diseases |
| title | Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases |
| title_full | Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases |
| title_fullStr | Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases |
| title_full_unstemmed | Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases |
| title_short | Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases |
| title_sort | chemical screening approaches enabling drug discovery of autophagy modulators for biomedical applications in human diseases |
| topic | autophagy autophagy reporter autophagy substrate autophagy modulator screening method neurodegenerative diseases |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00038/full |
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