Are protozoan metacaspases potential parasite killers?

Meslin, Benoît; Zalila, Habib; Fasel, Nicolás; Picot, Stéphane; Bienvenu, Anne‐Lise

doi:10.1186/1756-3305-4-26

Cited by 47 publications

(39 citation statements)

References 46 publications

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“…Meslin et al (55) reported the involvement of terpenoids in the activation of programmed cell death in Plasmodium species, and in the interference of one or more substances in the process of cell differentiation of the parasite, which has proven to be an extremely complex process, with fine-tuned regulation of gene expression, resulting in a turnover of proteins and destruction of organelles present in Plasmodium, as well as other species of pathogenic protists (56) .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the antiplasmodial and leishmanicidal potential of Myrciaria dubia (Myrtaceae) extract

Correia

Lima

Oliveira

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Introduction: Malaria and leishmaniasis are prevalent in tropical regions, which have environmental characteristics that are highly favorable to protozoa and vectors of these diseases; the transmission of these infections in sub-tropical regions, although recognized, represents only a small fraction of cases. Plants are constantly being used in the search for and acquisition of new drugs, and many compounds derived from them have been used to combat various diseases. In this study, we evaluated the action of the dichloromethanolic extract of Myrciaria dubia leaves against the protozoa Plasmodium falciparum, Leishmania amazonensis, Leishmania braziliensis, and Leishmania chagasi through bioassays. Methods: The extract from M. dubia was tested for its anti-P. falciparum activity in an anti-histidine-rich protein II immunosorbent assay. The antileishmanial assays were performed using the resazurin method, while cytotoxicity against human hepatoma (HepG2) strain was determined using the colorimetric MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide] method. Results: The M. dubia extract presented a half-maximal inhibitory concentration equal to 2.35 (1.05)μg/mL for P. falciparum, 190.73 (6.41) μg/mL for L. amazonensis, and greater than equal to 200µg/mL for L. chagasi and L. braziliensis strains. The cytotoxic concentration for 50% of the cells was above 500μg/mL for HepG2, indicating no toxicity and greater selectivity against parasites. Conclusions:The results obtained indicate the presence of antiplasmodial and leishmanicidal bioactive compounds in the dichloromethanolic extracts of M. dubia leaves, and point towards future studies to elucidate the mechanism of action for each physiological effect.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the antiplasmodial and leishmanicidal potential of Myrciaria dubia (Myrtaceae) extract

Correia

Lima

Oliveira

et al. 2016

Rev. Soc. Bras. Med. Trop.

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“…T. brucei expresses five isoforms (TbMCA 1–5) of this enzyme, with isoforms 2, 3 and 5 being validated as drug targets . While the precise role that metacaspases play in protozoa is yet to be fully understood, they have been implicated in programmed cell death . Owing to their apparent necessity in trypanosomes coupled to their absence in mammals, Berg et al.…”

Section: Kinetoplastids (Trypanosomiasis and Leishmaniasis)mentioning

confidence: 99%

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

Veale

2019

ChemMedChem

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The Pathogen Box is a 400‐strong collection of drug‐like compounds, selected for their potential against several of the world's most important neglected tropical diseases, including trypanosomiasis, leishmaniasis, cryptosporidiosis, toxoplasmosis, filariasis, schistosomiasis, dengue virus and trichuriasis, in addition to malaria and tuberculosis. This library represents an ensemble of numerous successful drug discovery programmes from around the globe, aimed at providing a powerful resource to stimulate open source drug discovery for diseases threatening the most vulnerable communities in the world. This review seeks to provide an in‐depth analysis of the literature pertaining to the compounds in the Pathogen Box, including structure–activity relationship highlights, mechanisms of action, related compounds with reported activity against different diseases, and, where appropriate, discussion on the known and putative targets of compounds, thereby providing context and increasing the accessibility of the Pathogen Box to the drug discovery community.

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“…Caspase-like activity is usually detected by studies using substrate-inhibition assays, however, these assays may not be absolutely specific for the clan CD cysteine proteases that the caspases belong to (discussed in [47]), and the involvement of metacaspases in apoptosis in P. falciparum has been contested [80] - although see [42,81]. Other proteases have now been identified as being involved in the apoptosis pathways of parasitic protists.…”

Section: Reviewmentioning

confidence: 99%

The first suicides: a legacy inherited by parasitic protozoans from prokaryote ancestors

Taylor-Brown

Hurd

2013

Parasites Vectors

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It is more than 25 years since the first report that a protozoan parasite could die by a process resulting in a morphological phenotype akin to apoptosis. Since then these phenotypes have been observed in many unicellular parasites, including trypanosomatids and apicomplexans, and experimental evidence concerning the molecular pathways that are involved is growing. These observations support the view that this form of programmed cell death is an ancient one that predates the evolution of multicellularity. Here we review various hypotheses that attempt to explain the origin of apoptosis, and look for support for these hypotheses amongst the parasitic protists as, with the exception of yeast, most of the work on death mechanisms in unicellular organisms has focussed on them. We examine the role that addiction modules may have played in the original eukaryote cell and the part played by mitochondria in the execution of present day cells, looking for examples from Leishmania spp. Trypanosoma spp. and Plasmodium spp. In addition, the expanding knowledge of proteases, nucleases and other molecules acting in protist execution pathways has enabled comparisons to be made with extant Archaea and bacteria and with biochemical pathways that evolved in metazoans. These comparisons lend support to the original sin hypothesis but also suggest that present-day death pathways may have had multifaceted beginnings.

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Are protozoan metacaspases potential parasite killers?

Cited by 47 publications

References 46 publications

Evaluation of the antiplasmodial and leishmanicidal potential of Myrciaria dubia (Myrtaceae) extract

Evaluation of the antiplasmodial and leishmanicidal potential of Myrciaria dubia (Myrtaceae) extract

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

The first suicides: a legacy inherited by parasitic protozoans from prokaryote ancestors

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