Abstract
The clostridial neurotoxins (CNTs) are among the most potent protein toxins known to humans. CNTs include seven serotypes (A~G) of botulinum toxins (BoNTs), which cause botulism, a flaccid paralysis, and tetanus toxin (TeNT), which causes spastic paralysis. BoNTs are classified as category A agent and may be used as potential bioterrorism weapons. On the other hand, the ability of an extremely low dosage of BoNTs (less than 1 ng) to cause reversible partial paralysis upon injection into muscle has turned BoNTs, in particular serotypes A and B, from deadly agents to novel therapeutic agents for treatment of a wide range of clinical conditions associated with involuntary muscle spasm and contractions. In addition to clinical use, they may also be used in cosmetics. Further indications for BoNTs will continue to be developed, although current BoNT therapies have encountered some limitations due to the pharmacological properties of BoNTs, such as their ability to elicit immunoresistance in patients upon periodical injections. This review summarizes the present knowledge of the mechanisms of action of CNTs, with particular focus on the mode of substrate recognition by CNT catalytic domains and knowledge regarding substrate recognition can be utilized to develop novel BoNT products to extend its usefulness in therapeutic interventions and overcome the immunoresistance problems.
Keywords: Botulinum toxins (BoNTs), Clostridial neurotoxins (CNTs), novel therapy development, substrate recognition.
Current Protein & Peptide Science
Title:Clostridial Neurotoxins: Mode of Substrate Recognition and Novel Therapy Development
Volume: 15 Issue: 5
Author(s): Sheng Chen
Affiliation:
Keywords: Botulinum toxins (BoNTs), Clostridial neurotoxins (CNTs), novel therapy development, substrate recognition.
Abstract: The clostridial neurotoxins (CNTs) are among the most potent protein toxins known to humans. CNTs include seven serotypes (A~G) of botulinum toxins (BoNTs), which cause botulism, a flaccid paralysis, and tetanus toxin (TeNT), which causes spastic paralysis. BoNTs are classified as category A agent and may be used as potential bioterrorism weapons. On the other hand, the ability of an extremely low dosage of BoNTs (less than 1 ng) to cause reversible partial paralysis upon injection into muscle has turned BoNTs, in particular serotypes A and B, from deadly agents to novel therapeutic agents for treatment of a wide range of clinical conditions associated with involuntary muscle spasm and contractions. In addition to clinical use, they may also be used in cosmetics. Further indications for BoNTs will continue to be developed, although current BoNT therapies have encountered some limitations due to the pharmacological properties of BoNTs, such as their ability to elicit immunoresistance in patients upon periodical injections. This review summarizes the present knowledge of the mechanisms of action of CNTs, with particular focus on the mode of substrate recognition by CNT catalytic domains and knowledge regarding substrate recognition can be utilized to develop novel BoNT products to extend its usefulness in therapeutic interventions and overcome the immunoresistance problems.
Export Options
About this article
Cite this article as:
Chen Sheng, Clostridial Neurotoxins: Mode of Substrate Recognition and Novel Therapy Development, Current Protein & Peptide Science 2014; 15 (5) . https://dx.doi.org/10.2174/13892037113146660086
DOI https://dx.doi.org/10.2174/13892037113146660086 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Role of Protein Conformational Dynamics and DNA Integrity in Relevance to Neuronal Cell Death in Neurodegeneration
Current Alzheimer Research Methionine Aminopeptidases as Potential Targets for Treatment of Gastrointestinal Cancers and other Tumors
Current Drug Targets Drug-Loaded Nanocarriers in Tumor Targeted Drug Delivery
Current Biotechnology The Medicinal Chemistry of Peptides
Current Medicinal Chemistry VIP in Neurological Diseases: More Than A Neuropeptide
Endocrine, Metabolic & Immune Disorders - Drug Targets Leptin and Interleukin-1β Modulate Neuronal Glutamate Release and Protect Against Glucose-Oxygen-Serum Deprivation
Current Neurovascular Research Malignant Mesothelioma: Cell Survival Pathways and Radiation Therapy
Current Respiratory Medicine Reviews Calcium Channel Subtypes and Exocytosis in Chromaffin Cells at Early Life
Current Molecular Pharmacology Lopinavir/Ritonavir Treatment Induces Oxidative Stress and Caspaseindependent Apoptosis in Human Glioblastoma U-87 MG Cell Line
Current HIV Research Effects of Vitamin A Deficiency and Opioids on Parvalbumin + Interneurons in the Hippocampus of the HIV-1 Transgenic Rat
Current HIV Research NMDA Receptors in Glial Cells: Pending Questions
Current Neuropharmacology P-glycoprotein Inhibition as a Therapeutic Approach for Overcoming Multidrug Resistance in Cancer: Current Status and Future Perspectives
Current Cancer Drug Targets Click Chemistry, A Potent Tool in Medicinal Sciences
Current Medicinal Chemistry Exploiting Internal Ribosome Entry Sites in Gene Therapy Vector Design
Current Gene Therapy Neurotoxicity by Synthetic Androgen Steroids: Oxidative Stress, Apoptosis, and Neuropathology: A Review
Current Neuropharmacology Biology of Cox-2: An Application in Cancer Therapeutics
Current Drug Targets Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions
Current Neuropharmacology From Natural Products to Designer Drugs: Development and Molecular Mechanisms Action of Novel Anti-Microtubule Breast Cancer Therapeutics
Current Topics in Medicinal Chemistry Identification of Disease States and Response to Therapy in Humans by Utilizing the Biomarker EGFR for Targeted Molecular Imaging
Current Protein & Peptide Science Experimental Models of Discovery: Prediction and Protection must Proceed “Hand-in-Hand”
Current Neurovascular Research