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Neurotoxin

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https://www.readbyqxmd.com/read/28647871/cytoskeleton-as-a-target-of-quinolinic-acid-neurotoxicity-insight-from-animal-models
#1
REVIEW
Paula Pierozan, Regina Pessoa-Pureur
Cytoskeletal proteins are increasingly recognized as having important roles as a target of the action of different neurotoxins. In the last years, several works of our group have shown that quinolinic acid (QUIN) was able to disrupt the homeostasis of the cytoskeleton of neural cells and this was associated with cell dysfunction and neurodegeneration. QUIN is an excitotoxic metabolite of tryptophan metabolism and its accumulation is associated with several neurodegenerative diseases. In the present review, we provide a comprehensive view of the actions of QUIN upstream of glutamate receptors, eliciting kinase/phosphatase signaling cascades that disrupt the homeostasis of the phosphorylation system associated with intermediate filament proteins of astrocytes and neurons...
June 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28645943/the-structure-of-the-tetanus-toxin-reveals-ph-mediated-domain-dynamics
#2
Geoffrey Masuyer, Julian Conrad, Pål Stenmark
The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a "closed" domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor...
June 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28645175/perturbation-to-cholesterol-at-the-neuromuscular-junction-confers-botulinum-neurotoxin-a-sensitivity-to-neonatal-mice
#3
Baskaran Thyagarajan, Joseph G Potian, Joseph J McArdle, Padmamalini Baskaran
Botulinum neurotoxin A (BoNT/A) cleaves SNAP25 at the motor nerve terminals (MNT) and inhibits stimulus evoked acetylcholine release (SEAR). This causes skeletal muscle paralysis. However, younger neonatal mice (<P7; less than 7 days old) are resistant to the neuroparalytic effects of BoNT/A. That is, in vivo injection of BoNT/A at the innervations of Extensor digitorum longus (EDL) muscle in the hindlimbs inhibited the toe spread reflex within 24 hours following BoNT/A injection in adult mouse and in older (> P7) neonatal mice younger than 7 days-age remained unaffected by BoNT/A injection...
June 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28639368/botulinum-toxin-state-of-the-art
#4
REVIEW
Joseph Jankovic
Botulinun neurotoxin (BoNT) has emerged as one of the most multipurpose therapeutic agents in modern medicine with more clinical applications than any other drug currently on the market. Initially developed in the treatment of strabismus and neurologic movement disorders, the use of botulinun neurotoxin has been expanding during the past 3 decades to include the treatment of a variety of ophthalmologic, gastrointestinal, urologic, orthopedic, dermatologic, dental, secretory, painful, cosmetic, and other conditions...
June 22, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28635651/effects-of-tetrodotoxin-in-mouse-models-of-visceral-pain
#5
Rafael González-Cano, Miguel Ángel Tejada, Antonia Artacho-Cordón, Francisco Rafael Nieto, José Manuel Entrena, John N Wood, Cruz Miguel Cendán
Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28634472/antifungal-activity-against-filamentous-fungi-of-ts1-a-multifunctional-toxin-from-tityus-serrulatus-scorpion-venom
#6
Welligton M Santussi, Karla C F Bordon, Ana P N Rodrigues Alves, Camila T Cologna, Suraia Said, Eliane C Arantes
Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28629806/prevalence-of-bleeding-complications-following-ultrasound-guided-botulinum-toxin-injections-in-patiens-on-anticoagulation-or-antiplatelet-therapy
#7
Jeffrey Lavallee, Regan Royer, Geoffrey Smith
BACKGROUND: Patients on anticoagulation or antiplatelet therapy may be at higher risk of bleeding complications following intramuscular chemodenervation injections. Musculoskeletal ultrasound may be able to reduce the risk of bleeding complications by providing real time visualization of vascular structures and post-injection monitoring. Limited data exist addressing risk of bleeding complications following ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures in the setting of anticoagulation or antiplatelet therapy...
June 16, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28627694/investigation-of-the-neuroprotective-effects-of-a-novel-synthetic-compound-via-the-mitochondrial-pathway
#8
Di Wang, Shuang Hu, Junrong Zhang, Qiuyue Li, Xinyu Liu, Yu Li
The present study aimed to investigate the neuroprotective effect of a novel synthetic compound (5zou) on differentiated PC12 cells against 6‑hydroxydopamine (6‑OHDA) and L‑glutamic acid (L‑Glu) neurotoxin‑induced cell injury and the potential mechanisms involved. 5zou is a 2, 2‑disubstituted 1,2‑dihydropyridine. PC12 cells were treated with 6‑OHDA and L‑Glu to establish neurotoxic cell models. MTT assay, DCFH‑DA staining, Fluo‑4‑AM staining, JC‑1 staining and western blotting were used to determine the changes in cell viability, intracellular reactive oxygen species concentration, Ca2+ influx, mitochondrial membrane potential and the protein expressions of B‑cell lymphoma‑2 (Bcl‑2) and B‑cell lymphoma‑extra large (Bcl‑xL)...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626912/structural-characterisation-of-acetogenins-from-annona-muricata-by-supercritical-fluid-chromatography-coupled-to-high-resolution-tandem-mass-spectrometry
#9
Laurent Laboureur, Natacha Bonneau, Pierre Champy, Alain Brunelle, David Touboul
INTRODUCTION: Acetogenins are plant polyketides known to be cytotoxic and proposed as antitumor candidates. They are also suspected to be alimentary neurotoxins. Their occurrence as complex mixtures renders their dereplication and structural identification difficult using liquid chromatography coupled to tandem mass spectrometry and efforts are required to improve the methodology. OBJECTIVE: To develop a supercritical fluid chromatography (SFC) high-resolution tandem mass spectrometry method, involving lithium post-column cationisation, for the structural characterisation of Annonaceous acetogenins in crude extracts...
June 19, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28625954/attenuation-of-cadmium-induced-decline-in-spatial-habituation-and-recognition-memory-by-long-term-administration-of-almond-and-walnut-supplementation-role-of-cholinergic-function
#10
Zehra Batool, Faiza Agha, Saara Ahmad, Laraib Liaquat, Saiqa Tabassum, Saima Khaliq, Lubna Anis, Irfan Sajid, Shaista Emad, Tahira Perveen, Saida Haider
Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats...
January 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28623709/the-mechanism-of-neuroprotective-action-of-natural-compounds
#11
REVIEW
Agnieszka Wąsik, Lucyna Antkiewicz-Michaluk
Disturbance of cerebral redox homeostasis is the primary cause of human neurodegenerative disorders, such as Parkinson's disease or Alzheimer's disease. Well known experimental research demonstrates that oxidative stress is a main cause of cell death. A high concentration of reactive oxygen and nitrogen species leads to damage of a lot of proteins, lipids and also DNA. Synthetic compounds used for the treatment in the neurodegenerative diseases failed to meet the hopes they had raised and often exhibit a number of side effects...
April 30, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28623170/nicotinic-acetylcholine-receptor-inhibitors-derived-from-snake-and-snail-venoms
#12
REVIEW
Sebastien Dutertre, Annette Nicke, Victor Tsetlin
The nicotinic acetylcholine receptor (nAChR) represents the prototype of ligand-gated ion channels. It is vital for neuromuscular transmission and an important regulator of neurotransmission. A variety of toxic compounds derived from diverse species target this receptor and have been of elemental importance in basic and applied research. They enabled milestone discoveries in pharmacology and biochemistry ranging from the original formulation of the receptor concept, the first isolation and structural analysis of a receptor protein (the nAChR) to the identification, localization, and differentiation of its diverse subtypes and their validation as a target for therapeutic intervention...
June 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28622274/a-role-for-neurokinin-1-receptor-neurons-in-the-rostral-ventromedial-medulla-in-the-development-of-chronic-postthoracotomy-pain
#13
Sergey G Khasabov, Jeffrey Chi-Fei Wang, Donald A Simone, Gary R Strichartz
Thoracotomy results in chronic postoperative pain (CPTP) in half of the cases. Earlier findings in rat models of persistent post-surgical pain suggest that spinal pathways are critical for pain onset but not its maintenance. Descending systems from the brain stem modulate nociceptive transmission in the spinal cord and contribute to persistent pain, but their role in chronic postoperative pain has not been studied. Here, we ablated pronociceptive neurokinin-1 receptor (NK-1R)-expressing neurons in the rat rostral ventromedial medulla (RVM) to identify their role in CPTP...
July 2017: Pain
https://www.readbyqxmd.com/read/28620274/influence-of-estrogen-modulation-on-glia-activation-in-a-murine-model-of-parkinson-s-disease
#14
Francesca Siani, Rosaria Greco, Giovanna Levandis, Cristina Ghezzi, Francesca Daviddi, Chiara Demartini, Elisabetta Vegeto, Marie-Thérèse Fuzzati-Armentero, Fabio Blandini
Epidemiological data suggest a sexual dimorphism in Parkinson disease (PD), with women showing lower risk of developing PD. Vulnerability of the nigrostriatal pathway may be influenced by exposure to estrogenic stimulation throughout fertile life. To further address this issue, we analyzed the progression of nigrostriatal damage, microglia and astrocyte activation and microglia polarization triggered by intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in male, female and ovariectomized (OVX) mice, as well as in OVX mice supplemented with 17βestradiol (OVX+E)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28617306/characterization-of-hemagglutinin-negative-botulinum-progenitor-toxins
#15
Suzanne R Kalb, Jakub Baudys, Theresa J Smith, Leonard A Smith, John R Barr
Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs), toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC), alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs) to cause hemagglutination...
June 15, 2017: Toxins
https://www.readbyqxmd.com/read/28614091/injectable-daxibotulinumtoxina-for-the-treatment-of-glabellar-lines-a-phase-2-randomized-dose-ranging-double-blind-multicenter-comparison-with-onabotulinumtoxina-and-placebo
#16
Jean Carruthers, Nowell Solish, Shannon Humphrey, Nathan Rosen, Channy Muhn, Vince Bertucci, Arthur Swift, Andrei Metelitsa, Roman G Rubio, Jacob Waugh, John Quiring, Gill Shears, Alastair Carruthers
BACKGROUND: Injectable daxibotulinumtoxinA (RT002) is an investigational botulinum toxin Type A in clinical development. It is formulated with a proprietary peptide and offers the potential of a longer acting neurotoxin therapy. OBJECTIVE: To compare the safety, efficacy, and duration of response of daxibotulinumtoxinA with onabotulinumtoxinA and placebo [www.clinicaltrials.gov NCT02303002]. METHODS: In this Phase 2, randomized, dose-ranging, parallel-group, double-blind, multicenter study, subjects with moderate or severe glabellar lines at maximum frown were randomly assigned to 20U, 40U, or 60U daxibotulinumtoxinA, 20U onabotulinumtoxinA, or placebo...
June 12, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28612294/the-potential-role-of-bmaa-in-neurodegeneration
#17
REVIEW
Tracie Caller, Patricia Henegan, Elijah Stommel
Neurodegenerative diseases are a major public health issue throughout the world with devastating effects on patients and families. Sporadic forms of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are generally thought to develop as a consequence of genetic susceptibility and environmental influences. A number of environmental triggers have been identified in association with amyotrophic lateral sclerosis and Parkinson's disease. We discuss the role of β-methylamino-L-alanine in the development of neurodegeneration and the potential importance of this neurotoxin as a risk for neurodegeneration...
June 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28612001/botulinum-toxin-off-label-use-in-dermatology-a-review
#18
REVIEW
Anna Campanati, Emanuela Martina, Katia Giuliodori, Veronica Consales, Ivan Bobyr, Annamaria Offidani
BACKGROUND: Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum which causes a flaccid muscle paralysis. It is currently used for aesthetic treatments and in the focal hyperhidrosis. Recently, botulinum toxin has also been used experimentally in many other dermatological conditions with good results. OBJECTIVE: To review and analyze the possible botulinum toxin off-label applications published. METHODS: A retrospective review of the published data was conducted...
March 2017: Skin Appendage Disorders
https://www.readbyqxmd.com/read/28606423/unraveling-the-presence-of-multi-class-toxins-from-trichodesmium-bloom-in-the-gulf-of-mannar-region-of-the-bay-of-bengal
#19
Sumathy Shunmugam, Manickam Gayathri, Nainangu Prasannabalaji, Nooruddin Thajuddin, Gangatharan Muralitharan
Trichodesmium is an enigmatic bloom forming, non-heterocystous cyanobacterium reported most frequently in the coastal waters of India. However, the toxigenic potential of this globally significant N2 fixing cyanobacterium has not been characterized. In this study, we report for the first time the presence of potent multi-class neurotoxins such as Anatoxin-a, Saxitoxins, Gonyautoxin and hepatotoxins like MC-LR, MC-YA from a bloom material of Trichodesmium sp. MBDU 524 collected at the Gulf of Mannar region. Toxins were determined using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) analysis of HPLC purified aqueous and solvent fractions...
June 9, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28605881/scorpion-neurotoxin-aait-expressing-beauveria-bassiana-enhances-the-virulence-against-aedes-albopictus-mosquitoes
#20
Sheng-Qun Deng, Qun-Di Cai, Ming-Zhi Deng, Qiang Huang, Hong-Juan Peng
To improve the insecticidal efficacy of this entomopathogen Beauveria bassiana, the fungus was genetically modified to express an insect-specific scorpion neurotoxin AaIT. The virulence of the recombinant B. bassiana strain (Bb-AaIT) against Aedes albopictus adults (which occurs via penetration through the cuticle during spore germination or by conidia ingestion), and the larvae (by conidia ingestion) was measured with bioassays. The median lethal concentration (LC50) of Bb-AaIT against A. albopictus larvae was 313...
December 2017: AMB Express
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