Re: Is actin the praziquantel receptor?

Tallima, Hatem; Ridi, Rashika El

doi:10.1016/j.ijantimicag.2007.08.002

Cited by 4 publications

(3 citation statements)

References 6 publications

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“…Therefore, reports of low drug efficacy [48–50] and schistosome resistance to the drug [39,51–55] have raised intense alarm. The likely possibility that PZQ binds and polymerizes schistosome and mammalian actin [56–60] should preclude its use in children, pregnant women, and individuals with vascular diseases [61] .…”

Section: Schistosomicidesmentioning

confidence: 99%

Novel Therapeutic and Prevention Approaches for Schistosomiasis: Review

Ridi

Tallima

2013

Journal of Advanced Research

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Schistosomiasis is a debilitating disease affecting approximately 600 million people in 74 developing countries, with 800 million, mostly children at risk. To circumvent the threat of having praziquantel (PZQ) as the only drug used for treatment, several PZQ derivatives were synthesized, and drugs destined for other parasites were used with success. A plethora of plant-derived oils and extracts were found to effectively kill juvenile and adult schistosomes, yet none was progressed to pre- and clinical studies except an oleo-gum resin extracted from the stem of Commiphora molmol , myrrh, which action was challenged in several trials. We have proposed an essential fatty acid, a component of our diet and cells, the polyunsaturated fatty acid arachidonic acid (ARA) as a remedy for schistosomiasis, due to its ability to activate the parasite tegument-bound neutral sphingomyelinase, with subsequent hydrolysis of the apical lipid bilayer sphingomyelin molecules, allowing access of specific antibody molecules, and eventual worm attrition. This concept was convincingly supported using larval and adult Schistosoma mansoni and Schistosoma haematobium worms in in vitro experiments, and in vivo studies in inbred mice and outbred hamsters. Even if ARA proves to be an entirely effective and safe therapy for schistosomiasis, it will not prevent reinfection, and accordingly, the need for developing an effective vaccine remains an urgent priority. Our studies have supported the status of S. mansoni calpain, glutathione-S-transferase, aldolase, triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, enolase, and 2-cys peroxiredoxin as vaccine candidates, as they are larval excreted-secreted products and, contrary to the surface membrane molecules, are entirely accessible to the host immune system effector elements. We have proposed that the use of these molecules, in conjunction with Th2 cytokines-inducing adjuvants for recruiting and activating eosinophils and basophils, will likely lead to development and implementation of a sterilizing vaccine in a near future.

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Section: Schistosomicidesmentioning

confidence: 99%

Novel Therapeutic and Prevention Approaches for Schistosomiasis: Review

Ridi

Tallima

2013

Journal of Advanced Research

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“…Amino acid microsequencing and immunogenicity studies indicated that PZQ preferably binds to schistosome actin at the exclusion of other adult worm surface membrane antigens. We have proposed that PZQ accesses actin of schistosomes and induces its polymerization, with subsequent parasite contraction and tegument disruption [38,39]. Cytochalasin B disrupts actin polymerization by capping the fast-growing end of actin filaments.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Praziquantel and Arachidonic Acid Combination — An Innovative Approach to the Treatment of Schistosomiasis

Tallima¹,

Hadley²,

Ridi³

2015

An Overview of Tropical Diseases

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Schistosomiasis is a debilitating disease caused by trematode worms of the genus Schistosoma. Three members Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum are responsible for the great majority of human infections.Schistosomiasis is widespread in sub-Saharan Africa, several countries of the Middle East, South America, and South-East Asia. Vaccination against the infection would be the most reliable way to combat the infection and decrease or interrupt its transmission, but a commercial vaccine is still unavailable. Praziquantel PZQ is the only drug considered for schistosomiasis treatment as it is effective against the major human schistosomes, commercially available, cost-affordable, and elicits limited side-effects. Several reports documented the highly significant PZQ efficacy in treatment of light infections in areas of low S. mansoni and S. haematobium endemicity and PZQ use. Chemotherapy with PZQ alone of patients residing in regions of high schistosome endemicity and afflicted with light, moderate, or heavy infection is not efficacious. Accordingly, we propose implementation of cost-affordable arachidonic acid ARA , a polyunsaturated omega-fatty acid and efficacious in vitro and in vivo schistosomicide, for oral therapy of children with Schistosoma mansoni and Schistosoma haematobium light infection, as adjunct to PZQ for cure of children with moderate and heavy infections, and for counteracting schistosome resistance to PZQ that arises in endemic areas exposed to repeated and intense PZQ mass treatment campaigns.

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“…Due to its hydrophobic nature and small size, PZQ inserts itself into the parasite outer lipid bilayer membrane, leading to its vacuolization, blebbing, and disruption [28]. Several reports documented the ability of PZQ to bind and polymerise actin [29][30][31][32][33][34]. Actin-based membrane skeleton (the fence) lies beneath the inner leaflet of the plasma membrane [35], and accordingly PZQ-parasite actin binding and subsequent polymerization may explain the severe muscle contraction and the paralysis worms undergo immediately upon exposure in vitro to PZQ.…”

Section: Praziquantelmentioning

confidence: 99%

Solving the Riddle of the Lung-Stage Schistosomula Paved the Way to a Novel Remedy and an Efficacious Vaccine for Schistosomiasis

Ridi¹,

Tallima²

2013

Parasitic Diseases - Schistosomiasis

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Please use Adobe Acrobat Reader to read this book chapter for free. Just open this same document with Adobe Reader. If you do not have it, you can download it here. You can freely access the chapter at the Web Viewer here. Parasitic Diseases-Schistosomiasis 180 Please use Adobe Acrobat Reader to read this book chapter for free. Just open this same document with Adobe Reader. If you do not have it, you can download it here. You can freely access the chapter at the Web Viewer here. Solving the Riddle of the Lung-Stage Schistosomula Paved the Way to a Novel Remedy and an Efficacious Vaccine...

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Re: Is actin the praziquantel receptor?

Cited by 4 publications

References 6 publications

Novel Therapeutic and Prevention Approaches for Schistosomiasis: Review

Novel Therapeutic and Prevention Approaches for Schistosomiasis: Review

Praziquantel and Arachidonic Acid Combination — An Innovative Approach to the Treatment of Schistosomiasis

Solving the Riddle of the Lung-Stage Schistosomula Paved the Way to a Novel Remedy and an Efficacious Vaccine for Schistosomiasis

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