Immunization does not interfere with uptake and transport by motor neurons of the binding fragment of tetanus toxin

2006 ◽  
Vol 83 (8) ◽  
pp. 1540-1543 ◽  
Author(s):  
Paul S. Fishman ◽  
Christopher C. Matthews ◽  
Deborah A. Parks ◽  
Michael Box ◽  
Neil F. Fairweather
Keyword(s):  
Motor Neurons ◽  
Tetanus Toxin ◽  
Uptake And Transport

Detoxified tetanus toxin (TETIM) – A superb nano-carrier for retro-axonal gene delivery to motor neurons in bypass of blood brain barriers

Toxicon ◽  
2019 ◽  
Vol 159 ◽  
pp. S12-S13
Author(s):  
Saak V. Ovsepian ◽  
MacDara Bodeker ◽  
Valerie B. O'Leary ◽  
J. Oliver Dolly
Keyword(s):  
Gene Delivery ◽  
Motor Neurons ◽  
Tetanus Toxin ◽  
Blood Brain ◽  
Brain Barriers

scholarly journals A Heterologous Reporter Defines the Role of the Tetanus Toxin Interchain Disulfide in Light-Chain Translocation

2015 ◽  
Vol 83 (7) ◽  
pp. 2714-2724 ◽  
Author(s):  
Madison Zuverink ◽  
Chen Chen ◽  
Amanda Przedpelski ◽  
Faith C. Blum ◽  
Joseph T. Barbieri
Keyword(s):  
Motor Neurons ◽  
Disulfide Bond ◽  
Light Chain ◽  
Tetanus Toxin ◽  
Thioredoxin Reductase ◽  
Single Chain ◽  
Intact Cells ◽  
Spastic Paralysis ◽  
Interchain Disulfide Bond ◽  
N Terminus

Botulinum neurotoxins (BoNTs) and tetanus toxin (TeNT) are the most potent toxins for humans and elicit unique pathologies due to their ability to traffic within motor neurons. BoNTs act locally within motor neurons to elicit flaccid paralysis, while retrograde TeNT traffics to inhibitory neurons within the central nervous system (CNS) to elicit spastic paralysis. BoNT and TeNT are dichain proteins linked by an interchain disulfide bond comprised of an N-terminal catalytic light chain (LC) and a C-terminal heavy chain (HC) that encodes an LC translocation domain (HCT) and a receptor-binding domain (HCR). LC translocation is the least understood property of toxin action, but it involves low pH, proteolysis, and an intact interchain disulfide bridge. Recently, Pirazzini et al. (FEBS Lett 587:150–155, 2013,http://dx.doi.org/10.1016/j.febslet.2012.11.007) observed that inhibitors of thioredoxin reductase (TrxR) blocked TeNT and BoNT action in cerebellar granular neurons. In the current study, an atoxic TeNT LC translocation reporter was engineered by fusing β-lactamase to the N terminus of TeNT [βlac-TeNT(RY)] to investigate LC translocation in primary cortical neurons and Neuro-2a cells. βlac-TeNT(RY) retained the interchain disulfide bond, showed ganglioside-dependent binding to neurons, required acidification to promote βlac translocation, and was sensitive to auranofin, an inhibitor of thioredoxin reductase. Mutation of βlac-TeNT(RY) at C439S and C467S eliminated the interchain disulfide bond and inhibited βlac translocation. These data support the requirement of an intact interchain disulfide for LC translocation and imply that disulfide reduction is a prerequisite for LC delivery into the host cytosol. The data also support a model that LC translocation proceeds from the C to the N terminus. βlac-TeNT(RY) is the first reporter system to measure translocation by an AB single-chain toxin in intact cells.

scholarly journals Analysis of retrograde transport in motor neurons reveals common endocytic carriers for tetanus toxin and neurotrophin receptor p75NTR

2002 ◽  
Vol 156 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Giovanna Lalli ◽  
Giampietro Schiavo
Keyword(s):  
Motor Neurons ◽  
Tetanus Toxin ◽  
Experimental System ◽  
Retrograde Transport ◽  
Endocytic Pathway ◽  
Neurotrophin Receptor ◽  
Tubular Structures ◽  
Growth And Survival ◽  
Membrane Compartments ◽  
The Central Nervous System

Axonal retrograde transport is essential for neuronal growth and survival. However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized. To shed light on this pathway, we established an experimental system for the visualization and the quantitative study of retrograde transport in living motor neurons based on a fluorescent fragment of tetanus toxin (TeNT HC). Morphological and kinetic analysis of TeNT HC retrograde carriers reveals two major groups of organelles: round vesicles and fast tubular structures. TeNT HC carriers lack markers of the classical endocytic pathway and are not acidified during axonal transport. Importantly, TeNT HC and NGF share the same retrograde transport organelles, which are characterized by the presence of the neurotrophin receptor p75NTR. Our results provide the first direct visualization of retrograde transport in living motor neurons, and reveal a novel retrograde route that could be used both by physiological ligands (i.e., neurotrophins) and TeNT to enter the central nervous system.

scholarly journals The effect of haloperidol, aminooxyacetic acid and (-)-nuciferine on prolonging survival time of mice with tetanus

2018 ◽  
Vol 72 (2) ◽  
pp. 122-128
Author(s):  
Indira Mujezinovic ◽  
Ahmed Smajlovic ◽  
Vitomir Cupic
Keyword(s):  
Survival Time ◽  
Motor Neurons ◽  
Tetanus Toxin ◽  
Synaptic Cleft ◽  
Aminooxyacetic Acid ◽  
Clostridium Tetani ◽  
Experimental Tetanus ◽  
Inhibitory Neurotransmitter ◽  
Average Survival ◽  
Characteristic Motor

Introduction. Tetanus, also known as lockjaw, is a very dangerous, infectious, acute, usually afebrile disease characterised by muscle spasms. The causative agent of the disease is the bacterium Clostridium tetani. This pathogen produces a specific neurotoxin, termed tetanus toxin, with two components: tetanospasmin and tetanolysin. Light chains of tetanospasmin cleavage synaptobrevin, which in turn prevent release of the inhibitory neurotransmitter GABA into the synaptic cleft. The ?-motor neurons are, therefore, under no inhibitory control, as a result of which they undergo sustained excitatory discharge causing the characteristic motor spasms of tetanus. Materials and Methods. In this research, we attempted to normalise disorders caused by tetanus toxin by using haloperidol (at doses of 4, 5, 6, 7 and 8 mg/kg b.w.), alone and in combination with (-)-nuciferine (at a dose of 5 mg/kg b.w.) or aminooxyacetic acid (at a dose of 20 mg/kg b.w.). Experiments were conducted on albino mice. Experimental tetanus was induced by application of tetanus toxin. Results and Conclusions. Application of haloperidol (alone and in combination with (-)-nuciferine and aminooxyacetic acid) was carried out 24 h following the application of tetanus toxin. It was found that haloperidol, given alone in a dose of 4 mg/kg, prolonged the average survival time of mice with experimental tetanus by 24.35 h compared to the control animals. Additionally, the combination of haloperidol with (-)-nuciferine slightly, but non-significantly, extended survival time , while the combination of haloperidol with aminooxyacetic acid produced the best effect on extension of survival time (mice survived on average 27.74 h longer than control mice).

Disorders Caused by Botulinum Toxin and Tetanus Toxin

2017 ◽  
Author(s):  
Carl E. Stafstrom
Keyword(s):  
Skeletal Muscle ◽  
Botulinum Toxin ◽  
Motor Neurons ◽  
Tetanus Toxin ◽  
Botulinum Neurotoxin ◽  
Acetylcholine Release ◽  
Neuromuscular Junctions ◽  
Muscle Rigidity ◽  
Inhibitory Neurotransmitters ◽  
Central Synapses

Anaerobic organisms of the genus Clostridia (C) can cause significant human disease. Exotoxins secreted by C botulinum and C tetani cause botulism and tetanus, respectively (summarized in Table 156.1). Botulinum neurotoxin causes neuromuscular blockade by interfering with vesicular acetylcholine release, leading to cholinergic blockade at the neuromuscular junctions of skeletal muscle, and consequently, symmetric flaccid paralysis. Tetanus toxin prevents release of inhibitory neurotransmitters at central synapses, leading to overactivity of motor neurons and muscle rigidity and spasms. This chapter reviews clinical features of botulism and tetanus and discusses their pathophysiological basis.

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