Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease
The carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts a neuroprotective effect in neurodegenerative diseases via the activation of signaling pathways related to neurotrophins, and also through inhibiting apoptotic cell death. Here, we demonstrate that Hc-TeTx preserves mo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/10/666 |
| _version_ | 1797550231460511744 |
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| author | Mireia Herrando-Grabulosa Caty Casas Kevin Talbot José Aguilera |
| author_facet | Mireia Herrando-Grabulosa Caty Casas Kevin Talbot José Aguilera |
| author_sort | Mireia Herrando-Grabulosa |
| collection | DOAJ |
| description | The carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts a neuroprotective effect in neurodegenerative diseases via the activation of signaling pathways related to neurotrophins, and also through inhibiting apoptotic cell death. Here, we demonstrate that Hc-TeTx preserves motoneurons from chronic excitotoxicity in an in vitro model of amyotrophic lateral sclerosis. Furthermore, we found that PI3-K/Akt pathway, but not p21ras/MAPK pathway, is involved in their beneficial effects under chronic excitotoxicity. Moreover, we corroborate the capacity of the Hc-TeTx to be transported retrogradely into the spinal motor neurons and also its capacity to bind to the motoneuron-like cell line NSC-34. These findings suggest a possible therapeutic tool to improve motoneuron preservation in neurodegenerative diseases such as amyotrophic lateral sclerosis. |
| first_indexed | 2024-03-10T15:26:32Z |
| format | Article |
| id | doaj.art-5a4784c2165b488391649e2ba54979c2 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T15:26:32Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-5a4784c2165b488391649e2ba54979c22023-11-20T17:59:40ZengMDPI AGToxins2072-66512020-10-01121066610.3390/toxins12100666Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron DiseaseMireia Herrando-Grabulosa0Caty Casas1Kevin Talbot2José Aguilera3Institute of Neurosciences, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainInstitute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UKInstitute of Neurosciences, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainThe carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts a neuroprotective effect in neurodegenerative diseases via the activation of signaling pathways related to neurotrophins, and also through inhibiting apoptotic cell death. Here, we demonstrate that Hc-TeTx preserves motoneurons from chronic excitotoxicity in an in vitro model of amyotrophic lateral sclerosis. Furthermore, we found that PI3-K/Akt pathway, but not p21ras/MAPK pathway, is involved in their beneficial effects under chronic excitotoxicity. Moreover, we corroborate the capacity of the Hc-TeTx to be transported retrogradely into the spinal motor neurons and also its capacity to bind to the motoneuron-like cell line NSC-34. These findings suggest a possible therapeutic tool to improve motoneuron preservation in neurodegenerative diseases such as amyotrophic lateral sclerosis.https://www.mdpi.com/2072-6651/12/10/666carboxyl-terminal domain of the heavy chain of tetanus toxinneuroprotectionexcitotoxicityspinal muscular atrophyamyotrophic lateral sclerosis |
| spellingShingle | Mireia Herrando-Grabulosa Caty Casas Kevin Talbot José Aguilera Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease Toxins carboxyl-terminal domain of the heavy chain of tetanus toxin neuroprotection excitotoxicity spinal muscular atrophy amyotrophic lateral sclerosis |
| title | Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease |
| title_full | Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease |
| title_fullStr | Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease |
| title_full_unstemmed | Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease |
| title_short | Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease |
| title_sort | neurotrophic properties of c terminal domain of the heavy chain of tetanus toxin on motor neuron disease |
| topic | carboxyl-terminal domain of the heavy chain of tetanus toxin neuroprotection excitotoxicity spinal muscular atrophy amyotrophic lateral sclerosis |
| url | https://www.mdpi.com/2072-6651/12/10/666 |
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