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Caspase-8 mediates inflammation and disease in rodent malaria

September 16, 2020 - 13:03 -- Open Access
Pereira LMN, Assis PA, Gazzinelli RT, et al.
Nat Commun. 2020 Sep 14;11(1):4596

Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM).

NOT Open Access | Blood-cerebrospinal fluid barrier: another site disrupted during experimental cerebral malaria caused by Plasmodium berghei ANKA

September 8, 2020 - 11:42 -- NOT Open Access
Ngo-Thanh H, Sasaki T, Suzue K, Yokoo H, Isoda K, Kamitani W, Shimokawa C, Hisaeda H, Imai T
Int J Parasitol. 2020 Aug 31:S0020-7519(20)30247-2

Cerebral malaria (CM) is one of the most severe pathologies of malaria; it induces neuro-cognitive sequelae and has a high mortality rate. Although many factors involved in the development of CM have been discovered, its pathogenic mechanisms are still not completely understood. Most studies on CM have focused on the blood-brain barrier (BBB), despite the importance of the blood-cerebrospinal fluid barrier (BCSFB), which protects the brain from peripheral inflammation.

Not Open Access | In vitro and in vivo evaluation of the antimalarial MMV665831 and structural analogs

September 5, 2020 - 15:53 -- NOT Open Access
Ding S, Fike KR, Klemba M, Carlier PR
Bioorg Med Chem Lett. 2020 Sep 1;30(17):127348

Antimalarial candidates possessing novel mechanisms of action are needed to control drug resistant Plasmodium falciparum. We were drawn to Malaria Box compound 1 (MMV665831) by virtue of its excellent in vitro potency, and twelve analogs were prepared to probe its structure–activity relationship. Modulation of the diethyl amino group was fruitful, producing compound 25, which was twice as potent as 1 against cultured parasites.

NOT Open Access | Half-Sandwich Cyclopentadienylruthenium(II) Complexes: A New Antimalarial Chemotype

August 25, 2020 - 15:34 -- NOT Open Access
Milheiro SA, Gonçalves J, Moreira R, et al.
Inorg Chem. 2020 Aug 24

A small library of "half-sandwich" cyclopentadienylruthenium(II) compounds of the general formula [(η5-C5R5)Ru(PPh3)(N-N)][PF6], a scaffold hitherto absent from the toolbox of antiplasmodials, was screened for activity against the blood stage of CQ-sensitive 3D7-GFP, CQ-resistant Dd2, and artemisinin-resistant IPC5202 Plasmodium falciparum strains and the liver stage of Plasmodium berghei.

Molecular determinants of SR-B1-dependent Plasmodium sporozoite entry into hepatocytes

August 13, 2020 - 11:43 -- Open Access
Langlois AC, Manzoni G, Vincensini L, Coppée R, Marinach C, Guérin M, Huby T, Carrière V, Cosset FL, Dreux M, Rubinstein E, Silvie O
Sci Rep. 2020 Aug 11;10(1):13509

Sporozoite forms of the Plasmodium parasite, the causative agent of malaria, are transmitted by mosquitoes and first infect the liver for an initial round of replication before parasite proliferation in the blood. The molecular mechanisms involved during sporozoite invasion of hepatocytes remain poorly understood. Two receptors of the Hepatitis C virus (HCV), the tetraspanin CD81 and the scavenger receptor class B type 1 (SR-B1), play an important role during the entry of Plasmodium sporozoites into hepatocytes.

Heparin Administered to Anopheles in Membrane Feeding Assays Blocks Plasmodium Development in the Mosquito

August 5, 2020 - 16:24 -- Open Access
Lantero E, Fernandes J, Aláez-Versón CR, Gomes J, Silveira H, Nogueira F, Fernàndez-Busquets X
Biomolecules. 2020 Aug 1;10(8):E1136

Innovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against Plasmodium parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with Plasmodium berghei-infected blood to Anopheles stephensi mosquitoes.

NOT Open Access | Virus-like particles expressing Plasmodium berghei MSP-8 induce protection against P. berghei infection

August 5, 2020 - 14:10 -- NOT Open Access
Lee SH, Chu KB, Kang HJ, Basak S, Kim MJ, Park H, Jin H, Moon EK, Quan FS
Parasite Immunol. 2020 Aug 1:e12781

Merozoite surface protein 8 (MSP‐8) of Plasmodium parasites play an important role in erythrocyte invasion and is a potential malaria vaccine candidate.

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