alexa The Nervous System: An Ideal Therapeutic Target for Anti-Schistosomal Drug Discovery | OMICS International
ISSN: 2329-9088
Tropical Medicine & Surgery
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

The Nervous System: An Ideal Therapeutic Target for Anti-Schistosomal Drug Discovery

Shi-Bin Cheng*

Department of Pediatrics, Women and Infants Hospital, Alpert Medical School, Brown University, USA

*Corresponding Author:
Shi-Bin Cheng
Department of Pediatrics
Women and Infants Hospital
Alpert, Medical School
Brown University, Providence
RI 02903, USA
Tel: 401-274-1122
E-mail: [email protected]

Received Date: January 02, 2013; Accepted Date: January 05, 2013; Published Date: January 28, 2013

Citation: Cheng SB (2013) The Nervous System: An Ideal Therapeutic Target for Anti-Schistosomal Drug Discovery. Tropical Medicine & Surgery 1:e103. doi: 10.4172/2329-9088.1000e103

Copyright: © 2013 Cheng SB. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Tropical Medicine & Surgery

Schistosomiasis is a parasitic disease that afflicts over 200 million people worldwide, causing visceral organ disturbance, and impairing growth and cognitive development in children [1]. The etiological agents of human schistosomiasis are the blood flukes of the genus Schistosoma, including S. mansoni, S. haematobium, and S. japonicum. S. mansoni is blamed for over 90% of all human schistosomiasis [2]. Epidemiological evidence reveals that schistosomiasis is typically endemic in tropical countries in Africa, the Caribbean, South America, Southeastern Asia and Middle East, especially in the regions where the intermediate snail host that carries the parasite. Because no vaccine is available for Schistosoma, chemotherapeutic intervention is still the primary option for schistosomiasis treatment. The treatment of human schistosomiasis relies solely on Praziquantel which has been widely used for over three decades. However, emergence of drug resistance in the worms has ignited enthusiasm to search for alternative drug candidates.

To date, there have been numerous candidate molecules that were proposed as potential chemotherapeutic targets for treating schistosomiasis. These molecules are involved in a variety of survivalrelated machineries of the worm, including redox metabolism (e.g. thioredoxin glutathione reductase) [3,4], ion channels (e.g. calcium channel subunits) [5], chromatin modification (e.g. histone acetyltransferases and deacetylase) [6], metal homeostasis (e.g. phytochelatin synthase) [7,8], protein maturation (e.g. methionine aminopeptidase) [9], and cell signaling (e.g. cAMP-dependent protein kinase and cyclophilin) [10,11]. In contrast to these potential therapeutic strategies, the nervous system of the helminth parasites has been successfully employed as a target by anthelmintics currently in use, including ivermectin, levamisole and monepantel [1]. All of these drugs act on neuroreceptors in the neuromuscular system of the worm, which results in disrupting the neural and neuromuscular transmission, and consequently paralyzing and killing the worm. Ivermectin not only eliminates nematodes, but also trematodes (Fasciola spp., Schistosoma spp.) as well [1].

Schistosoma has a well developed nervous system that consists of a simple brain and several pairs of longitudinal nerve cords (the central nervous system) and a peripheral network that innervates almost all body tissues, especially the tegument, the somatic musculature and the suckers [1,2]. Biogenic amines, including serotonin, dopamine and 5-hydroxytryptamine, are the major neurotransmitters in the nervous system of schistosomes and function as pivotal modulators of neuromuscular transmission, regulating locomotion, attachment to the host and many other behaviors that are essential to the parasite survival in the host [1]. Thus, Biosynthetic enzymes, receptors and transporters of biogenic amines may be aimed as the targets for the development of chemotherapeutic agents against schistosomes. Drug screens have revealed that blockers for serotonergic and dopaminergic receptors and serotonin transporter are the potent disruptors that inhibit schistosome motility [1]. Serotonergic and dopaminergic receptors belong to the members of the super family of G Protein- Coupled Receptors (GPCRs). Recently, Ribeiro et al. have cloned a novel Schistosoma mansoni G protein-coupled receptor (SmGPR-3) [2]. SmGPR-3 was activated by dopamine and other catecholamines, resulting in a strong effect on the motility of larval schistosomes [2]. Immuno staining showed the localization of SmGPR-3 in the central nervous system and the peripheral plexuses innervating the musculature, the caecum, the tubercles and the male reproductive system of Schistosoma mansoni [2]. Since SmGPR-3 is substantially different from dopamine receptor of the mammalian host, this novel protein may be employed as a potential target for developing new schistosome-specific drugs. However, which G protein is recruited by SmGPR-3, how SmGPR-3 undergoes trafficking, endocytosis and degradation, and how SmGPR-3 signals remain yet to be investigated.

GPCRs constitute the largest family of cell surface receptors which share a common topology of seven transmembrane domains and modulate a variety of cell activities [12]. GPCRs are the targets of nearly half drugs currently in use and for the development of new therapeutics that treat a wide range of human diseases [12]. Regulation of surface expression, endocytosis, recycling and degradation of GPCRs involves a number of machineries that spatiotemporally mediate GPCRspromoted cell signaling [13,14]. Thus, all these machineries could be targeted for drug development. Moreover, the significant evolutionary difference in the structures of GPCRs between schistosome and the host allows developing drugs that specifically kill schistosome but cause less side-effect in the host [1]. To date, most of anthelmintic drugs currently in use act on the nervous system of helminth parasites [1]. Likewise, GPCRs in the nervous system of schistosome is a promising therapeutic target for anti-schistosomal drug discovery.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 11950
  • [From(publication date):
    February-2013 - Apr 21, 2018]
  • Breakdown by view type
  • HTML page views : 8152
  • PDF downloads : 3798
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version