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Virulence Dec 2023, a polyphyletic Gram-positive taxon of bacteria, is classified purely by their ability to produce botulinum neurotoxin (BoNT). BoNT is the primary virulence factor and... (Review)
Review
, a polyphyletic Gram-positive taxon of bacteria, is classified purely by their ability to produce botulinum neurotoxin (BoNT). BoNT is the primary virulence factor and the causative agent of botulism. A potentially fatal disease, botulism is classically characterized by a symmetrical descending flaccid paralysis, which is left untreated can lead to respiratory failure and death. Botulism cases are classified into three main forms dependent on the nature of intoxication; foodborne, wound and infant. The BoNT, regarded as the most potent biological substance known, is a zinc metalloprotease that specifically cleaves SNARE proteins at neuromuscular junctions, preventing exocytosis of neurotransmitters, leading to muscle paralysis. The BoNT is now used to treat numerous medical conditions caused by overactive or spastic muscles and is extensively used in the cosmetic industry due to its high specificity and the exceedingly small doses needed to exert long-lasting pharmacological effects. Additionally, the ability to form endospores is critical to the pathogenicity of the bacteria. Disease transmission is often facilitated via the metabolically dormant spores that are highly resistant to environment stresses, allowing persistence in the environment in unfavourable conditions. Infant and wound botulism infections are initiated upon germination of the spores into neurotoxin producing vegetative cells, whereas foodborne botulism is attributed to ingestion of preformed BoNT. is a saprophytic bacterium, thought to have evolved its potent neurotoxin to establish a source of nutrients by killing its host.
Topics: Infant; Humans; Clostridium botulinum; Botulism; Virulence; Neurotoxins; Botulinum Toxins
PubMed: 37157163
DOI: 10.1080/21505594.2023.2205251 -
Toxins Jan 2023Botulinum toxin (BoNT) is an anaerobic rod-shaped-neurotoxin produced by Clostridium botulinum, that has both therapeutic and lethal applications. BoNT injection is the... (Review)
Review
Botulinum toxin (BoNT) is an anaerobic rod-shaped-neurotoxin produced by Clostridium botulinum, that has both therapeutic and lethal applications. BoNT injection is the most popular cosmetic procedure worldwide with various applications. Patients with dynamic wrinkles in areas such as the glabella, forehead, peri-orbital lines, nasal rhytides, and perioral rhytides are indicated. Excessive contraction of muscles or hyperactivity of specific muscles such as bulky masseters, cobble stone chins, gummy smiles, asymmetric smiles, and depressed mouth corners can achieve esthetic results by targeting the precise muscles. Patients with hypertrophic submandibular glands and parotid glands can also benefit esthetically. There are several FDA-approved BoNTs (obabotuli-numtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, letibotulinumtoxinA, prabotulinumtox-inA, daxibotulinumtoxinA, rimbotulinumtoxinB) and novel BoNTs on the market. This paper is a narrative review of the consensus statements of expert practitioners and various literature on the injection points and techniques, highlighting both the Asian and Caucasian population separately. This paper can serve as a practical illustrative guide and reference for optimal, safe injection areas and effective doses for application of BoNT in the face and oral and maxillofacial area. The history of BoNT indications, contraindications, and complications, and the merits of ultrasonography (US)-assisted injections are also discussed.
Topics: Humans; Botulinum Toxins, Type A; Face; Forehead; Neurotoxins; Cosmetic Techniques; Esthetics; Neuromuscular Agents
PubMed: 36828397
DOI: 10.3390/toxins15020082 -
Skin Therapy Letter Jul 2023Botulinum toxin A (BoNTA) is produced by Clostridium botulinum and widely used for aesthetic indications requiring neuromuscular blockade. For dynamic facial lines,... (Review)
Review
Botulinum toxin A (BoNTA) is produced by Clostridium botulinum and widely used for aesthetic indications requiring neuromuscular blockade. For dynamic facial lines, BoNTA is effective and safe, but also temporary, requiring repeat injections approximately every 3-4 months for maintenance of effects. There is a desire by both patients and providers for a longer-lasting neurotoxin to prevent periods of suboptimal correction. Approved by the US Food and Drug Administration (FDA) in September 2022, daxibotulinumtoxinA for injection (DAXI or Daxxify™) is the first long-lasting BoNTA formulated with a 150-kDa BoNTA (RTT150) and proprietary stabilizing excipient peptide (RTP004) in place of human serum albumin. DAXI is approved for treatment of moderate to severe glabellar lines. The median duration of effect was 6 months and results lasted as long as 9 months in some patients. Its unique formulation and prolonged effectiveness positions DAXI as a safe, novel BoNTA for improved durability and patient satisfaction.
Topics: Humans; Botulinum Toxins, Type A; Face; Neurotoxins; Patient Satisfaction; Skin Aging
PubMed: 37440610
DOI: No ID Found -
Journal of Neurochemistry Sep 2021Tetanus is a deadly but preventable disease caused by a protein neurotoxin produced by Clostridium tetani. Spores of C. tetani may contaminate a necrotic wound and... (Review)
Review
Tetanus is a deadly but preventable disease caused by a protein neurotoxin produced by Clostridium tetani. Spores of C. tetani may contaminate a necrotic wound and germinate into a vegetative bacterium that releases a toxin, termed tetanus neurotoxin (TeNT). TeNT enters the general circulation, binds to peripheral motor neurons and sensory neurons, and is transported retroaxonally to the spinal cord. It then enters inhibitory interneurons and blocks the release of glycine or GABA causing a spastic paralysis. This review attempts to correlate the metalloprotease activity of TeNT and its trafficking and localization into the vertebrate body to the nature and sequence of appearance of the symptoms of tetanus.
Topics: Animals; Brain; Humans; Neurotoxins; Peripheral Nerves; Spinal Cord; Tetanus; Tetanus Toxin; Tetanus Toxoid
PubMed: 33629408
DOI: 10.1111/jnc.15330 -
Pharmacological Reviews Apr 2017The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their... (Review)
Review
The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology.
Topics: Animals; Botulinum Toxins; Humans; Neurotoxins
PubMed: 28356439
DOI: 10.1124/pr.116.012658 -
Tidsskrift For Den Norske Laegeforening... Nov 2018Facial paralysis can be a stigmatising condition, and in many cases it may affect the closing function of the eye, facial expression, the nasal airway passage, language... (Review)
Review
Facial paralysis can be a stigmatising condition, and in many cases it may affect the closing function of the eye, facial expression, the nasal airway passage, language and nutritional intake to varying degrees. For the majority of patients, treatment methods exist that may improve function and quality of life. This article aims to provide a review of relevant surgical reconstruction methods and treatment options for patients with facial paralysis.
Topics: Botulinum Toxins; Facial Paralysis; Humans; Neurotoxins; Plastic Surgery Procedures
PubMed: 30421736
DOI: 10.4045/tidsskr.17.1023 -
Archives of Toxicology Jun 2022Tetanus and botulinum neurotoxins cause the neuroparalytic syndromes of tetanus and botulism, respectively, by delivering inside different types of neurons,... (Review)
Review
Tetanus and botulinum neurotoxins cause the neuroparalytic syndromes of tetanus and botulism, respectively, by delivering inside different types of neurons, metalloproteases specifically cleaving the SNARE proteins that are essential for the release of neurotransmitters. Research on their mechanism of action is intensively carried out in order to devise improved therapies based on antibodies and chemical drugs. Recently, major results have been obtained with human monoclonal antibodies and with single chain antibodies that have allowed one to neutralize the metalloprotease activity of botulinum neurotoxin type A1 inside neurons. In addition, a method has been devised to induce a rapid molecular evolution of the metalloprotease domain of botulinum neurotoxin followed by selection driven to re-target the metalloprotease activity versus novel targets with respect to the SNARE proteins. At the same time, an intense and wide spectrum clinical research on novel therapeutics based on botulinum neurotoxins is carried out, which are also reviewed here.
Topics: Botulinum Toxins, Type A; Clostridium botulinum; Humans; Neurotoxins; SNARE Proteins; Tetanus
PubMed: 35333944
DOI: 10.1007/s00204-022-03271-9 -
Toxins Jan 2021Since its initial approval in 1989 by the US Food and Drug Administration for the treatment of blepharospasm and other facial spasms, botulinum toxin (BoNT) has evolved... (Review)
Review
Since its initial approval in 1989 by the US Food and Drug Administration for the treatment of blepharospasm and other facial spasms, botulinum toxin (BoNT) has evolved into a therapeutic modality for a variety of neurological and non-neurological disorders. With respect to neurologic movement disorders, BoNT has been reported to be effective for the treatment of dystonia, bruxism, tremors, tics, myoclonus, restless legs syndrome, tardive dyskinesia, and a variety of symptoms associated with Parkinson's disease. More recently, research with BoNT has expanded beyond its use as a powerful muscle relaxant and a peripherally active drug to its potential central nervous system applications in the treatment of neurodegenerative disorders. Although BoNT is the most potent biologic toxin, when it is administered by knowledgeable and experienced clinicians, it is one of the safest therapeutic agents in clinical use. The primary aim of this article is to provide an update on recent advances in BoNT research with a focus on novel applications in the treatment of movement disorders. This comprehensive review of the literature provides a critical review of evidence-based clinical trials and highlights recent innovative pilot studies.
Topics: Botulinum Toxins; Dyskinesias; Humans; Movement Disorders; Neurotoxins; Restless Legs Syndrome
PubMed: 33430071
DOI: 10.3390/toxins13010042 -
Nature Reviews. Drug Discovery Sep 2018Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis... (Review)
Review
Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis represent a major socio-economic challenge in view of their high prevalence yet poor treatment. They are often called 'proteinopathies' owing to the presence of misfolded and aggregated proteins that lose their physiological roles and acquire neurotoxic properties. One reason underlying the accumulation and spread of oligomeric forms of neurotoxic proteins is insufficient clearance by the autophagic-lysosomal network. Several other clearance pathways are also compromised in NDAs: chaperone-mediated autophagy, the ubiquitin-proteasome system, extracellular clearance by proteases and extrusion into the circulation via the blood-brain barrier and glymphatic system. This article focuses on emerging mechanisms for promoting the clearance of neurotoxic proteins, a strategy that may curtail the onset and slow the progression of NDAs.
Topics: Aging; Animals; Autophagy; Humans; Neurodegenerative Diseases; Neurotoxins; Proteasome Endopeptidase Complex; Ubiquitin
PubMed: 30116051
DOI: 10.1038/nrd.2018.109 -
Toxins Mar 2016Botulinum neurotoxin has revolutionized the treatment of spasticity and is now administered worldwide. There are currently three leading botulinum neurotoxin type A... (Review)
Review
Botulinum neurotoxin has revolutionized the treatment of spasticity and is now administered worldwide. There are currently three leading botulinum neurotoxin type A products available in the Western Hemisphere: onabotulinum toxin-A (ONA) Botox(®), abobotulinum toxin-A (ABO), Dysport(®), and incobotulinum toxin A (INCO, Xeomin(®)). Although the efficacies are similar, there is an intense debate regarding the comparability of various preparations. Here we will address the clinical issues of potency and conversion ratios, as well as safety issues such as toxin spread and immunogenicity, to provide guidance for BoNT-A use in clinical practice. INCO was shown to be as effective as ONA with a comparable adverse event profile when a clinical conversion ratio of 1:1 was used. The available clinical and preclinical data suggest that a conversion ratio ABO:ONA of 3:1-or even lower-could be appropriate for treating spasticity, cervical dystonia, and blepharospasm or hemifacial spasm. A higher conversion ratio may lead to an overdosing of ABO. While uncommon, distant spread may occur; however, several factors other than the pharmaceutical preparation are thought to affect spread. Finally, whereas the three products have similar efficacy when properly dosed, ABO has a better cost-efficacy profile.
Topics: Acetylcholine Release Inhibitors; Animals; Botulinum Toxins, Type A; Dystonic Disorders; Humans; Muscle Spasticity; Neuromuscular Agents; Neurotoxins
PubMed: 26959061
DOI: 10.3390/toxins8030065