ArticlePloS one2009
A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Screening the Global Health Priority Box against Plasmodium berghei liver stage parasites using an inexpensive luciferase detection protocol.Malaria journal · 2024Article
- Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.International journal of molecular sciences · 2024Review
- Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections.Expert opinion on therapeutic targets · 2022Review
- Maria M. Mota: BringingFrontiers in cellular and infection microbiology · 2022Article
- Malaria parasite plasmepsins: More than just plain old degradative pepsins.The Journal of biological chemistry · 2020Review
- Article
- γ-Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct.EMBO molecular medicine · 2017Article
- Differential Inhibition of Signal Peptide Peptidase Family Members by Established γ-Secretase Inhibitors.PloS one · 2015Article
- Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis.Biochemical and biophysical research communications · 2014Article
- The roles of intramembrane proteases in protozoan parasites.Biochimica et biophysica acta · 2013Review
- γ-Secretase inhibitors and modulators.Biochimica et biophysica acta · 2013Review
- Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito.BMC genomics · 2013Article
- Quantification of sporozoite invasion, migration, and development by microscopy and flow cytometry.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Article
- Activity of a trisubstituted pyrrole in inhibiting sporozoite invasion and blocking malaria infection.Antimicrobial agents and chemotherapy · 2010Article
- Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.PloS one · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. LY411,575 was found to prevent Plasmodium's normal development in the liver, with an IC(50) of approximately 80 nM, without affecting hepatocyte invasion by the parasite. In vivo results with a rodent model of malaria showed that LY411,575 decreases the parasite load in the liver and increases by 55% the resistance of mice to cerebral malaria, one of the most severe malaria-associated syndromes. Our data show that LY411,575 does not exert its effect via the Notch signaling pathway suggesting that it may interfere with Plasmodium development through an inhibition of the parasite's signal peptide peptidase. We therefore propose that selective signal peptide peptidase inhibitors could be potentially used for preventive treatment of malaria in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.