3177dfd98b19182eab6bfa61ec65b04d toxins_a2020v12n10p666.pdf 9ac75f80770c760c9064c3d8807f6f57461d7b54 toxins_a2020v12n10p666.pdf c71864bdbbdfbc94568be7cb0ae5a303b26a58d74a5d9d3a8db91c4b7445e6de toxins_a2020v12n10p666.pdf Title: Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease Subject: 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. Keywords: carboxyl-terminal domain of the heavy chain of tetanus toxin; neuroprotection; excitotoxicity; spinal muscular atrophy; amyotrophic lateral sclerosis Author: Mireia Herrando-Grabulosa, Caty Casas, Kevin Talbot and José Aguilera Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Sat Oct 24 04:40:34 2020 CEST ModDate: Sat Oct 24 05:11:13 2020 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1530904 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 PUXWWS+Pxsy Type 1 Builtin yes yes no 15 0 MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 19 0 OSGJBT+URWPalladioL-Ital Type 1 Custom yes yes no 23 0 PLHIOB+URWPalladioL-Bold Type 1 Custom yes yes no 28 0 HJSSVG+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 HAKARX+Rpxr Type 1 Builtin yes yes no 36 0 CUAJJQ+Pxbsy Type 1 Builtin yes yes no 40 0 DVMWWR+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 71 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 75 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 79 0 TGMEOR+Rpcxr Type 1 Builtin yes yes no 86 0 LEVXPH+EURM10 Type 1 Builtin yes yes no 90 0 AELJPI+PalatinoLinotype TrueType WinAnsi yes yes no 100 0 AELKBK+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 103 0 AELKCL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 106 0 AELKIK+TimesNewRoman CID TrueType Identity-H yes yes yes 109 0 AELJPH+PalatinoLinotype CID TrueType Identity-H yes yes yes 123 0 AELJPI+PalatinoLinotype TrueType WinAnsi yes yes no 129 0 AELKBK+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 132 0 AELKCL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 135 0 AELKIK+TimesNewRoman CID TrueType Identity-H yes yes yes 138 0 AELJPH+PalatinoLinotype CID TrueType Identity-H yes yes yes 151 0 AELJPI+PalatinoLinotype TrueType WinAnsi yes yes no 157 0 AELKBK+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 160 0 AELKCL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 163 0 AELKIK+TimesNewRoman CID TrueType Identity-H yes yes yes 166 0 AELJPH+PalatinoLinotype CID TrueType Identity-H yes yes yes 179 0 AELJPI+PalatinoLinotype TrueType WinAnsi yes yes no 185 0 AELKBK+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 188 0 AELKCL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 191 0 AELKIK+TimesNewRoman CID TrueType Identity-H yes yes yes 194 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 04:24:43 CEST RepresentationInformation: toxins_a2020v12n10p666.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 11:39:37 CEST Size: 1530904 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 359 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Purification and Fluorescence Labeling of Recombinant Protein Hc-TeTx Destination: subsection.2.1 Item: Title: Membrane Motoneuron Binding and Retrograde Transport of Recombinant Hc-TeTx Protein Destination: subsection.2.2 Item: Title: Motor Neuron Preservation under Chronic Excitotoxicity Destination: subsection.2.3 Item: Title: Signaling Cascade Induced by Hc-TeTx under Chronic Excitotoxicity Destination: subsection.2.4 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Recombinant Hc-TeTx Protein Purification Destination: subsection.4.1 Item: Title: Hc-TeTx Retrogade Transport Destination: subsection.4.2 Item: Title: NSC-34 Cell Culture Destination: subsection.4.3 Item: Title: Spinal Cord Organotypic Culture Destination: subsection.4.4 Item: Title: Motor Neuron Counting Destination: subsection.4.5 Item: Title: Immunofluorescence Destination: subsection.4.6 Item: Title: Statistical Analysis Destination: subsection.4.7 Item: Title: References Destination: subsection.4.7 Info: Title: Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease Author: Mireia Herrando-Grabulosa, Caty Casas, Kevin Talbot and José Aguilera Subject: 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. 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