Heat Shock Proteins as Targets for Novel Antimalarial Drug Discovery

Daniyan, Michael Oluwatoyin

doi:10.1007/978-3-030-78397-6_9

Cited by 4 publications

(8 citation statements)

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“…Several reports have shown that heat shock proteins are promising antimalarial drug targets ( Pesce et al, 2010 ; Shonhai, 2010 ; Shrestha et al, 2016 ; Daniyan and Blatch, 2017 ; Daniyan et al, 2019b ; Daniyan, 2021 ). Despite the potential for compensatory upregulation of some heat shock proteins when one is inhibited (e.g., Hsp90 and Hsp70) ( Posfai et al, 2018 ), the essentiality of some members of the heat shock proteins family, their unique functional features, and their ability to form functional networks, not only make their inhibition lethal but that such inhibition could cause a wave of deleterious consequences on the down-stream biochemical processes that these functional networks influence ( Pavithra et al, 2007 ; Daniyan et al, 2019a ; Daniyan and Ojo, 2019 ).…”

Section: Potential Usefulness Of Known Chaperones Targeted Small Mole...mentioning

confidence: 99%

“…Today, small molecule inhibition of plasmodial heat shock proteins has shown promise in reversing P. falciparum - induced drug resistance, while also synergizing with traditional antimalarial drugs ( Shahinas et al, 2013b ; Cockburn et al, 2014 ; Posfai et al, 2018 ). Chalcones, polyphenols, terpenoids, alkaloids, and peptides are among the well-tested classes of small molecule inhibitors of heat shock proteins Table 1 [reviewed here ( Anokwuru et al, 2021 ; Daniyan, 2021 )]. While there are evidence that some may help in preventing the breakdown of the blood-brain barrier (BBB) ( Kam et al, 2012 ), their potential usefulness in cerebral malaria is largely unexplored.…”

Section: Potential Usefulness Of Known Chaperones Targeted Small Mole...mentioning

confidence: 99%

“…Malaria is most common in rural, indigenous, and impoverished zones of Africa, Asia, and the tropics of America ( Monteiro et al, 2014 ; Talapko et al, 2019 ). Prior to the advent of the COVID-19 pandemic, the fight against malaria infection appears to have been gaining success with noticeable decreases in the number of reported infections and deaths when compared to the previous year ( Daniyan, 2021 ). However, the disruption in all malaria intervention areas, including prevention, diagnosis, treatment, elimination, and surveillance, occasioned by the pandemic, has led to marked increases in reported cases and associated mortality ( Daniyan, 2021 ; WHO, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Prior to the advent of the COVID-19 pandemic, the fight against malaria infection appears to have been gaining success with noticeable decreases in the number of reported infections and deaths when compared to the previous year ( Daniyan, 2021 ). However, the disruption in all malaria intervention areas, including prevention, diagnosis, treatment, elimination, and surveillance, occasioned by the pandemic, has led to marked increases in reported cases and associated mortality ( Daniyan, 2021 ; WHO, 2021 ). The year 2021 world malaria reports estimated 241 million malaria cases and 627,000 deaths, representing 14 million more cases and 69,000 more deaths in 2020, with about 7.5% of these deaths linked to COVID-19 associated disruption ( WHO, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Neurotransmitters and molecular chaperones interactions in cerebral malaria: Is there a missing link?

Daniyan

Fisusi

Adeoye

2022

Front. Mol. Biosci.

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Plasmodium falciparum is responsible for the most severe and deadliest human malaria infection. The most serious complication of this infection is cerebral malaria. Among the proposed hypotheses that seek to explain the manifestation of the neurological syndrome in cerebral malaria is the vascular occlusion/sequestration/mechanic hypothesis, the cytokine storm or inflammatory theory, or a combination of both. Unfortunately, despite the increasing volume of scientific information on cerebral malaria, our understanding of its pathophysiologic mechanism(s) is still very limited. In a bid to maintain its survival and development, P. falciparum exports a large number of proteins into the cytosol of the infected host red blood cell. Prominent among these are the P. falciparum erythrocytes membrane protein 1 (PfEMP1), P. falciparum histidine-rich protein II (PfHRP2), and P. falciparum heat shock proteins 70-x (PfHsp70-x). Functional activities and interaction of these proteins with one another and with recruited host resident proteins are critical factors in the pathology of malaria in general and cerebral malaria in particular. Furthermore, several neurological impairments, including cognitive, behavioral, and motor dysfunctions, are known to be associated with cerebral malaria. Also, the available evidence has implicated glutamate and glutamatergic pathways, coupled with a resultant alteration in serotonin, dopamine, norepinephrine, and histamine production. While seeking to improve our understanding of the pathophysiology of cerebral malaria, this article seeks to explore the possible links between host/parasite chaperones, and neurotransmitters, in relation to other molecular players in the pathology of cerebral malaria, to explore such links in antimalarial drug discovery.

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Section: Potential Usefulness Of Known Chaperones Targeted Small Mole...mentioning

confidence: 99%

Section: Potential Usefulness Of Known Chaperones Targeted Small Mole...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neurotransmitters and molecular chaperones interactions in cerebral malaria: Is there a missing link?

Daniyan

Fisusi

Adeoye

2022

Front. Mol. Biosci.

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“…Survival of the malaria parasite inside the host and the vector depends on the action of molecular chaperones. The emergence of resistance to the most commonly used antimalarial drugs, coupled with the difficulty in producing an effective vaccine, resulted in an urgent need to develop drugs targeted against novel chemotherapeutic targets [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Hsp90 and Associated Co-Chaperones of the Malaria Parasite

et al. 2022

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Heat shock protein 90 (Hsp90) is one of the major guardians of cellular protein homeostasis, through its specialized molecular chaperone properties. While Hsp90 has been extensively studied in many prokaryotic and higher eukaryotic model organisms, its structural, functional, and biological properties in parasitic protozoans are less well defined. Hsp90 collaborates with a wide range of co-chaperones that fine-tune its protein folding pathway. Co-chaperones play many roles in the regulation of Hsp90, including selective targeting of client proteins, and the modulation of its ATPase activity, conformational changes, and post-translational modifications. Plasmodium falciparum is responsible for the most lethal form of human malaria. The survival of the malaria parasite inside the host and the vector depends on the action of molecular chaperones. The major cytosolic P. falciparum Hsp90 (PfHsp90) is known to play an essential role in the development of the parasite, particularly during the intra-erythrocytic stage in the human host. Although PfHsp90 shares significant sequence and structural similarity with human Hsp90, it has several major structural and functional differences. Furthermore, its co-chaperone network appears to be substantially different to that of the human host, with the potential absence of a key homolog. Indeed, PfHsp90 and its interface with co-chaperones represent potential drug targets for antimalarial drug discovery. In this review, we critically summarize the current understanding of the properties of Hsp90, and the associated co-chaperones of the malaria parasite.

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