The ultimate fate determinants of drug induced cell-death mechanisms in Trypanosomatids
Chemotherapy constitutes a major part of modern-day therapy for infectious and chronic diseases. A drug is said to be effective if it can inhibit its target, induce stress, and thereby trigger an array of cell death pathways in the form of programmed cell death, autophagy, necrosis, etc. Chemotherap...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320721000026 |
| _version_ | 1818640760536301568 |
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| author | Payel Das Saradindu Saha Somdeb BoseDasgupta |
| author_facet | Payel Das Saradindu Saha Somdeb BoseDasgupta |
| author_sort | Payel Das |
| collection | DOAJ |
| description | Chemotherapy constitutes a major part of modern-day therapy for infectious and chronic diseases. A drug is said to be effective if it can inhibit its target, induce stress, and thereby trigger an array of cell death pathways in the form of programmed cell death, autophagy, necrosis, etc. Chemotherapy is the only treatment choice against trypanosomatid diseases like Leishmaniasis, Chagas disease, and sleeping sickness. Anti-trypanosomatid drugs can induce various cell death phenotypes depending upon the drug dose and growth stage of the parasites. The mechanisms and pathways triggering cell death in Trypanosomatids serve to help identify potential targets for the development of effective anti-trypanosomatids. Studies show that the key proteins involved in cell death of trypanosomatids are metacaspases, Endonuclease G, Apoptosis-Inducing Factor, cysteine proteases, serine proteases, antioxidant systems, etc. Unlike higher eukaryotes, these organisms either lack the complete set of effectors involved in cell death pathways, or are yet to be deciphered. A detailed summary of the existing knowledge of different drug-induced cell death pathways would help identify the lacuna in each of these pathways and therefore open new avenues for research and thereby new therapeutic targets to explore. The cell death pathway associated complexities in metazoans are absent in trypanosomatids; hence this summary can also help understand the trigger points as well as cross-talk between these pathways. Here we provide an in-depth overview of the existing knowledge of these drug-induced trypanosomatid cell death pathways, describe their associated physiological changes, and suggest potential interconnections amongst them. |
| first_indexed | 2024-12-16T23:16:24Z |
| format | Article |
| id | doaj.art-1832b987cf844992951bd6c8e6e103f8 |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-12-16T23:16:24Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-1832b987cf844992951bd6c8e6e103f82022-12-21T22:12:16ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072021-04-01158191The ultimate fate determinants of drug induced cell-death mechanisms in TrypanosomatidsPayel Das0Saradindu Saha1Somdeb BoseDasgupta2Molecular Immunology and Cellular Microbiology Laboratory, Department of Biotechnology, Indian Institute of Technology, Kharagpur, IndiaMolecular Immunology and Cellular Microbiology Laboratory, Department of Biotechnology, Indian Institute of Technology, Kharagpur, IndiaCorresponding author.; Molecular Immunology and Cellular Microbiology Laboratory, Department of Biotechnology, Indian Institute of Technology, Kharagpur, IndiaChemotherapy constitutes a major part of modern-day therapy for infectious and chronic diseases. A drug is said to be effective if it can inhibit its target, induce stress, and thereby trigger an array of cell death pathways in the form of programmed cell death, autophagy, necrosis, etc. Chemotherapy is the only treatment choice against trypanosomatid diseases like Leishmaniasis, Chagas disease, and sleeping sickness. Anti-trypanosomatid drugs can induce various cell death phenotypes depending upon the drug dose and growth stage of the parasites. The mechanisms and pathways triggering cell death in Trypanosomatids serve to help identify potential targets for the development of effective anti-trypanosomatids. Studies show that the key proteins involved in cell death of trypanosomatids are metacaspases, Endonuclease G, Apoptosis-Inducing Factor, cysteine proteases, serine proteases, antioxidant systems, etc. Unlike higher eukaryotes, these organisms either lack the complete set of effectors involved in cell death pathways, or are yet to be deciphered. A detailed summary of the existing knowledge of different drug-induced cell death pathways would help identify the lacuna in each of these pathways and therefore open new avenues for research and thereby new therapeutic targets to explore. The cell death pathway associated complexities in metazoans are absent in trypanosomatids; hence this summary can also help understand the trigger points as well as cross-talk between these pathways. Here we provide an in-depth overview of the existing knowledge of these drug-induced trypanosomatid cell death pathways, describe their associated physiological changes, and suggest potential interconnections amongst them.http://www.sciencedirect.com/science/article/pii/S2211320721000026TrypanosomatidsRegulated cell-deathAutophagyNecrosis |
| spellingShingle | Payel Das Saradindu Saha Somdeb BoseDasgupta The ultimate fate determinants of drug induced cell-death mechanisms in Trypanosomatids International Journal for Parasitology: Drugs and Drug Resistance Trypanosomatids Regulated cell-death Autophagy Necrosis |
| title | The ultimate fate determinants of drug induced cell-death mechanisms in Trypanosomatids |
| title_full | The ultimate fate determinants of drug induced cell-death mechanisms in Trypanosomatids |
| title_fullStr | The ultimate fate determinants of drug induced cell-death mechanisms in Trypanosomatids |
| title_full_unstemmed | The ultimate fate determinants of drug induced cell-death mechanisms in Trypanosomatids |
| title_short | The ultimate fate determinants of drug induced cell-death mechanisms in Trypanosomatids |
| title_sort | ultimate fate determinants of drug induced cell death mechanisms in trypanosomatids |
| topic | Trypanosomatids Regulated cell-death Autophagy Necrosis |
| url | http://www.sciencedirect.com/science/article/pii/S2211320721000026 |
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