Modeling and targeting an essential metabolic pathway of Plasmodium falciparum in apicoplast using Petri nets

Gupta, Sakshi; Singh, Gajendra Pratap; Kumawat, Sunita

doi:10.1007/s11766-022-4413-x

Cited by 6 publications

(2 citation statements)

References 48 publications

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“…However, research is still ongoing to develop potential inhibitors against them [9]. Recently, computational studies employing Petri net analysis on FabD, FabG, and FabF revealed that impinging their activities leads to deadlock in the FAS II pathway [98]. Tis is important as similar studies could help unravel the complexities of metabolic networks and pinpoint key druggable enzymes for developing new antimalarial drugs.…”

Section: Inhibitors Of the Fatty Acid Synthesis Malaria Parasitesmentioning

confidence: 99%

Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Plasmodium falciparum Parasites

Mamudu,

Tebamifor,

Sule

et al. 2024

Advances in Pharmacological and Pharmaceutical Sciences

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The discovery of a relict plastid, also known as an apicoplast (apicomplexan plastid), that houses housekeeping processes and metabolic pathways critical to Plasmodium parasites’ survival has prompted increased research on identifying potent inhibitors that can impinge on apicoplast-localised processes. The apicoplast is absent in humans, yet it is proposed to originate from the eukaryote’s secondary endosymbiosis of a primary symbiont. This symbiotic relationship provides a favourable microenvironment for metabolic processes such as haem biosynthesis, Fe-S cluster synthesis, isoprenoid biosynthesis, fatty acid synthesis, and housekeeping processes such as DNA replication, transcription, and translation, distinct from analogous mammalian processes. Recent advancements in comprehending the biology of the apicoplast reveal it as a vulnerable organelle for malaria parasites, offering numerous potential targets for effective antimalarial therapies. We provide an overview of the metabolic processes occurring in the apicoplast and discuss the organelle as a viable antimalarial target in light of current advances in drug discovery. We further highlighted the relevance of these metabolic processes to Plasmodium falciparum during the different stages of the lifecycle.

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Section: Inhibitors Of the Fatty Acid Synthesis Malaria Parasitesmentioning

confidence: 99%

Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Plasmodium falciparum Parasites

Mamudu,

Tebamifor,

Sule

et al. 2024

Advances in Pharmacological and Pharmaceutical Sciences

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show abstract

“…'As a result, lncRNAs play a crucial role in organisms' growth, development, ageing, and death [79]. Therefore, further study is needed using other mathematical techniques, e.g., Petri Nets, and Graph Theory [80,81,82,83,84,85], to explore the critical role of lncRNAs in intestinal disorder and their potential roles as a therapy. LIMMA package was used to analyze data and quantify differentially expressed genes.…”

Section: Limitation Of Studymentioning

confidence: 99%

Entamoeba histolytica HM-1: IMSS gene expression profiling identifies key hub genes, potential biomarkers, and pathways in Amoebiasis infection: a systematic network meta-analysis

et al. 2022

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Entamoeba histolytica (E. histolytica) is an anaerobic parasite that causes Amoebiasis in the intestine or extraintestinal, with immunology, genetics, and environmental variables all playing a part in the disease's development, but its molecular mechanism is unknown. One of the primary obstacles in understanding the etiology of Amoebiasis will be identifying the genetics profiling that controls the amoebiasis network. By examining the gene expression profile of Amoebiasis and comparing it to healthy controls, we were able to identify differentially expressed genes (DEGs). Differentially expressed genes were used to build the amoebiasis protein interaction network and calculated its network topological properties. We discovered that nine key hub genes(KHGs) are JUN, PTGS2, FCGR3A, MNDA, CYBB, EGR1, CCL2, TLR8, and LRRK2 genes. The genes JUN and EGR1 were transcriptional factors (TFs) and up-regulated, others down-regulated. hsa-miR-155-5p,hsa-miR-101-3p,hsa-miR-124-3p,hsa-miR-26b-5p and hsa-miR-16-5p are also among the essential miRNAs that have been demonstrated to be targeted by key hub genes. These KHGs were primarily enriched in the IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway. miRNAs were grouped in various pathways, focusing on the TGF−beta signaling pathway, Human immunodeficiency virus 1 infection, Insulin signaling pathway, Signaling pathways regulating pluripotency of stem cells, etc. Amoebiasis KHGs (JUN, PTGS2, CCL2, MNDA) and their associated miRNAs are the primary targets for therapeutic methods and possible biomarkers. Furthermore, we identified drugs for genes JUN, PTGS2, FCGR3A, CCL2, and LRRK2. KHGs, on the other hand, required experimental validation to prove their efficacy.

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Enzymes of Isoprenoid Biosynthesis and Control of Malarial Parasite Plasmodium falciparum

Alkurbi,

Alghamdi,

Aslam

et al. 2024

Drug Targets for Plasmodium Falciparum: Historic to Future Perspectives

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Modeling and targeting an essential metabolic pathway of Plasmodium falciparum in apicoplast using Petri nets

Cited by 6 publications

References 48 publications

Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Plasmodium falciparum Parasites

Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Plasmodium falciparum Parasites

Entamoeba histolytica HM-1: IMSS gene expression profiling identifies key hub genes, potential biomarkers, and pathways in Amoebiasis infection: a systematic network meta-analysis

Enzymes of Isoprenoid Biosynthesis and Control of Malarial Parasite Plasmodium falciparum

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