The C‐terminal fragment of the heavy chain of the tetanus toxin (Hc‐TeTx) improves motor activity and neuronal morphology in the limbic system of aged mice

Synapse ◽  
2020 ◽  
Author(s):  
Ruben Vazquez‐Roque ◽  
Mariana Pacheco‐Flores ◽  
Julio Cesar Penagos‐Corzo ◽  
Gonzalo Flores ◽  
José Aguilera ◽  
...  
Keyword(s):  
Motor Activity ◽  
Limbic System ◽  
Heavy Chain ◽  
Tetanus Toxin ◽  
Neuronal Morphology ◽  
Aged Mice ◽  
Terminal Fragment

C-terminal fragment of tetanus toxin heavy chain modulates sphingomyelinase activity in neuronal preparations

Toxicon ◽  
2008 ◽  
Vol 51 ◽  
pp. 2-3
Author(s):  
Cubí Piqué Roger ◽  
Herrando Grabulosa Mireia ◽  
Aguilera Ávila José ◽  
Gil Giró Carles
Keyword(s):  
Heavy Chain ◽  
Tetanus Toxin ◽  
Terminal Fragment

scholarly journals Therapeutic Assay with the Non-toxic C-Terminal Fragment of Tetanus Toxin (TTC) in Transgenic Murine Models of Prion Disease

2021 ◽  
Author(s):  
Marina Betancor ◽  
Laura Moreno-Martínez ◽  
Óscar López-Pérez ◽  
Alicia Otero ◽  
Adelaida Hernaiz ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Prion Disease ◽  
Tetanus Toxin ◽  
Neuronal Survival ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Murine Models ◽  
Terminal Fragment ◽  
Lateral Sclerosis

AbstractThe non-toxic C-terminal fragment of the tetanus toxin (TTC) has been described as a neuroprotective molecule since it binds to Trk receptors and activates Trk-dependent signaling, activating neuronal survival pathways and inhibiting apoptosis. Previous in vivo studies have demonstrated the ability of this molecule to increase mice survival, inhibit apoptosis and regulate autophagy in murine models of neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrPC) into an abnormal and misfolded isoform known as PrPSc. These diseases share different pathological features with other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease or Alzheimer’s disease. Hitherto, there are no effective therapies to treat prion diseases. Here, we present a pilot study to test the therapeutic potential of TTC to treat prion diseases. C57BL6 wild-type mice and the transgenic mice Tg338, which overexpress PrPC, were intracerebrally inoculated with scrapie prions and then subjected to a treatment consisting of repeated intramuscular injections of TTC. Our results indicate that TTC displays neuroprotective effects in the murine models of prion disease reducing apoptosis, regulating autophagy and therefore increasing neuronal survival, although TTC did not increase survival time in these models.

Development of an improved tetanus vaccine composed of the heavy chain of the tetanus toxin molecule

Toxicon ◽  
1997 ◽  
Vol 35 (4) ◽  
pp. 483
Author(s):  
M. Matsuda ◽  
M. Takahashi ◽  
D. Lei ◽  
N. Sugimoto
Keyword(s):  
Heavy Chain ◽  
Tetanus Toxin ◽  
Toxin Molecule ◽  
Tetanus Vaccine

The effects of amphetamine exposure on juvenile rats on the neuronal morphology of the limbic system at prepubertal, pubertal and postpubertal ages

2016 ◽  
Vol 77 ◽  
pp. 68-77 ◽  
Author(s):  
Hiram Tendilla-Beltrán ◽  
Luis Enrique Arroyo-García ◽  
Alfonso Diaz ◽  
Israel Camacho-Abrego ◽  
Fidel de la Cruz ◽  
...  
Keyword(s):  
Limbic System ◽  
Neuronal Morphology ◽  
Juvenile Rats

HC fragment (C-terminal portion of the heavy chain) of tetanus toxin activates protein kinase C isoforms and phosphoproteins involved in signal transduction

2001 ◽  
Vol 356 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Carles GIL ◽  
Imane CHAIB-OUKADOUR ◽  
Juan BLASI ◽  
José AGUILERA
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Phosphorylation ◽  
Heavy Chain ◽  
Tetanus Toxin ◽  
Signal Transduction Pathways ◽  
Terminal Portion ◽  
Kinase C ◽  
Pkc Isoforms

A recent report [Gil, Chaib-Oukadour, Pelliccioni and Aguilera (2000) FEBS Lett. 481, 177–182] describes activation of signal transduction pathways by tetanus toxin (TeTx), a Zn2+-dependent endopeptidase synthesized by the Clostridium tetani bacillus, which is responsible for tetanus disease. In the present work, specific activation of protein kinase C (PKC) isoforms and of intracellular signal-transduction pathways, which include nerve-growth-factor (NGF) receptor trkA, phospholipase C(PLC)γ-1 and extracellular regulated kinases (ERKs) 1 and 2, by the recombinant C-terminal portion of the TeTx heavy chain (HC-TeTx) is reported. The activation of PKC isoforms was assessed through their translocation from the soluble (cytosolic) compartment to the membranous compartment, showing that clear translocation of PKC-α, −β, −γ and −δ isoforms exists, whereas PKC-∊ showed a slight decrease in its soluble fraction immunoreactivity. The PKC-∊ isoform showed no consistent response. Using immunoprecipitation assays against phosphotyrosine residues, time- and dose-dependent increases in tyrosine phosphorylation were observed in the trkA receptor, PLCγ-1 and ERK-1/2. The effects shown by the HC-TeTx fragment on tyrosine phosphorylation were compared with the effects produced by NGF. The trkA and ERK-1/2 activation were corroborated using phospho-specific antibodies against trkA phosphorylated on Tyr490, and antibodies against Thr/Tyr phosphorylated ERK-1/2. Moreover, PLCγ-1 phosphorylation was supported by its HC-TeTx-induced translocation to the membranous compartment, an event related to PLCγ-1 activation. Since HC-TeTx is the domain responsible for membrane binding and lacks catalytic activity, the activations described here must be exclusively triggered by the interaction of TeTx with a membrane component.

scholarly journals Surface topography of histidine residues of tetanus toxin probed by immobilized-metal-ion affinity chromatography

1992 ◽  
Vol 285 (1) ◽  
pp. 9-12 ◽  
Author(s):  
O Rossetto ◽  
G Schiavo ◽  
P Polverino de Laureto ◽  
S Fabbiani ◽  
C Montecucco
Keyword(s):  
Affinity Chromatography ◽  
Heavy Chain ◽  
Light Chain ◽  
Efficient Method ◽  
Tetanus Toxin ◽  
Metal Ion ◽  
Histidine Residues ◽  
Botulinum Neurotoxins ◽  
Matrix Bound ◽  
Metal Ion Affinity Chromatography

Tetanus toxin contains 14 histidine residues: six of them are localized in the light chain (L), one is present in the N-terminal half of the heavy chain (HN) and the remaining seven histidines are localized in the C-terminal half of the heavy chain (Hc). Using immobilized-metal-ion affinity chromatography with Chelating Superose-Zn(II), we show that histidines of Hc are exposed to the protein surface and are responsible for the binding of tetanus toxin and of Hc to the immobilized metal. The histidines of the L chain are not available for co-ordination of matrix-bound Zn2+; however, two of them and three of the histidines of fragment Hc are accessible to diethyl pyrocarbonate. Chromatography on Superose-Zn(II) is also shown to be a simple and efficient method for the rapid isolation of tetanus toxin and of its Hc fragment, which can be extended to the botulinum neurotoxins.

Expression of fragment C of tetanus toxin fused to a carboxyl-terminal fragment of diphtheria toxin in Salmonella typhi CVD 908 vaccine strain

Vaccine ◽  
1995 ◽  
Vol 13 (16) ◽  
pp. 1596-1602 ◽  
Author(s):  
Oscar G. Gómez-Duarte ◽  
James Galen ◽  
Steven N. Chatfield ◽  
Rino Rappuoli ◽  
Leon Eidels ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Tetanus Toxin ◽  
Diphtheria Toxin ◽  
Salmonella Typhi ◽  
Terminal Fragment ◽  
Carboxyl Terminal

scholarly journals retroLEAP: rAAV-based retrograde trans-synaptic labeling, expression and perturbation

2019 ◽  
Author(s):  
Janine K Reinert ◽  
Ivo Sonntag ◽  
Hannah Sonntag ◽  
Rolf Sprengel ◽  
Patric Pelzer ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Heavy Chain ◽  
Tetanus Toxin ◽  
Brain Regions ◽  
Nervous Systems ◽  
Novel Approach

AbstractIdentifying and manipulating synaptically connected neurons across brain regions remains a core challenge in understanding complex nervous systems. RetroLEAP is a novel approach for retrograde trans-synaptic Labelling, Expression And Perturbation. GFP-dependent recombinase (Flp-DOG) detects trans-synaptic transfer of GFP-tetanus toxin heavy chain fusion protein (GFP-TTC) and activates expression of any gene of interest in synaptically connected cells. RetroLEAP overcomes existing limitations, is non-toxic, highly flexible, efficient, sensitive and easy to implement.

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