The Role of Metacaspases and Other Proteins Involved in the Apoptosis of Leishmania: Review Article

Background: Apoptosis, a determined form of programmed cell death (PCD), occurs in multi-cellular and single-celled organisms. Given that a general understanding of apoptosis in single-cell Leishmania is crucial for designing disease control policies, we reviewed the apoptosis mechanism and the proteins involved. Methods: The information was obtained from articles published in PubMed, SciELO, Science Direct, Scopus, Google Scholar, and Web of Science databases (1998-2021). Search terms used were” apoptosis” or” Leishmaniasis”. Results: The 77 subjects were included in the study that revealed the significance of the apoptosis process for Leishmania survival. Although, various stimuli induce Leishmania apoptosis, the proteins involved in apoptosis have been poorly understood. Metacaspases in Leishmania instead of caspase and death receptors in mammals play the same role in the PCD pathways. Also, other apoptotic proteins in Leishmania such as endonuclease G (EndoG), caspases- like cysteine proteases, TSN (Tudor Staphylococcal Nuclease), and Zinnia endonuclease 1 (ZEN1) lead to phenotype similar to mammalian apoptosis. Furthermore, there are differences in these mechanisms between the different species of Leishmania and studies to illustrate downstream events related to the serine phosphatidylcholine exposure, cytochrome C secretion, etc. remain an ongoing challenge. Conclusion: Determining the essential regulatory proteins in the Leishmania apoptosis and the specific present of metacaspases in parasite, is effective for designing new therapeutic strategies against leishmaniasis and vaccine development.