Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease.
Amyotrophic Lateral Sclerosis
/ drug therapy
Animals
Cell Line
Mice
Motor Neurons
/ drug effects
Neuroprotective Agents
/ chemistry
Peptide Fragments
/ chemistry
Phosphatidylinositol 3-Kinase
/ metabolism
Protein Domains
Proto-Oncogene Proteins c-akt
/ metabolism
Rats, Sprague-Dawley
Recombinant Proteins
/ pharmacology
Signal Transduction
Spinal Cord
/ drug effects
Tetanus Toxin
/ chemistry
Tissue Culture Techniques
amyotrophic lateral sclerosis
carboxyl-terminal domain of the heavy chain of tetanus toxin
excitotoxicity
neuroprotection
spinal muscular atrophy
Journal
Toxins
ISSN: 2072-6651
Titre abrégé: Toxins (Basel)
Pays: Switzerland
ID NLM: 101530765
Informations de publication
Date de publication:
21 10 2020
21 10 2020
Historique:
received:
16
09
2020
revised:
13
10
2020
accepted:
18
10
2020
entrez:
24
10
2020
pubmed:
25
10
2020
medline:
17
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33096857
pii: toxins12100666
doi: 10.3390/toxins12100666
pmc: PMC7589688
pii:
doi:
Substances chimiques
Neuroprotective Agents
0
Peptide Fragments
0
Recombinant Proteins
0
Tetanus Toxin
0
tetanus toxin fragment C
0
Phosphatidylinositol 3-Kinase
EC 2.7.1.137
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministerio de Ciencia e Innovación
ID : SAF2013-43900-R
Pays : International
Organisme : Ministerior de Ciencia e Innovación
ID : SAF2016-8027-R
Pays : International
Références
Science. 1975 May 30;188(4191):945-7
pubmed: 49080
J Neurochem. 2013 Jan;124(1):36-44
pubmed: 23106494
Orphanet J Rare Dis. 2011 Mar 21;6:10
pubmed: 21418619
Mol Biol Cell. 2001 Oct;12(10):2947-60
pubmed: 11598183
Eur J Biochem. 1986 Jan 15;154(2):403-7
pubmed: 3943536
Folia Neuropathol. 2005;43(1):7-13
pubmed: 15827885
Orphanet J Rare Dis. 2009 Feb 03;4:3
pubmed: 19192301
Nat Rev Neurol. 2011 Nov;7(11):616-30
pubmed: 22051914
Neurosci Res. 2009 Sep;65(1):98-106
pubmed: 19523997
Lancet Neurol. 2017 Jul;16(7):505-512
pubmed: 28522181
Trends Microbiol. 2003 Sep;11(9):431-7
pubmed: 13678859
N Engl J Med. 1992 May 28;326(22):1464-8
pubmed: 1349424
Neuron. 2006 Oct 19;52(2):293-305
pubmed: 17046692
J Neurochem. 2000 May;74(5):1941-50
pubmed: 10800937
Neuroscience. 1990;34(1):251-63
pubmed: 1691466
Front Mol Neurosci. 2016 Aug 24;9:76
pubmed: 27605908
Ultrastruct Pathol. 2005 Sep-Oct;29(5):331-9
pubmed: 16257859
J Neurochem. 2004 Sep;90(5):1227-36
pubmed: 15312177
Antioxid Redox Signal. 2009 Jul;11(7):1587-602
pubmed: 19413484
Restor Neurol Neurosci. 2012;30(1):69-80
pubmed: 22124037
J Neurol. 2018 Oct;265(10):2454-2462
pubmed: 30054789
Ther Adv Neurol Disord. 2009 Sep;2(5):319-26
pubmed: 21180622
Eur J Neurosci. 1998 Aug;10(8):2481-9
pubmed: 9767379
J Biol Chem. 2011 Sep 30;286(39):34015-22
pubmed: 21849494
J Cell Biol. 2002 Jan 21;156(2):233-9
pubmed: 11807088
J Mol Med (Berl). 2010 Mar;88(3):297-308
pubmed: 19921501
Spine (Phila Pa 1976). 2018 Mar 15;43(6):E327-E333
pubmed: 28767631
J Biol Chem. 1993 May 25;268(15):11188-92
pubmed: 8388386
Biochem J. 2001 May 15;356(Pt 1):97-103
pubmed: 11336640
Ann Neurol. 1995 Jul;38(1):73-84
pubmed: 7611729
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6591-5
pubmed: 8393571
Biochem J. 2003 Jul 15;373(Pt 2):613-20
pubmed: 12710887
J Neurochem. 1977 Mar;28(3):529-42
pubmed: 67185
Mol Cell Neurosci. 2005 Dec;30(4):572-82
pubmed: 16456925
Mol Cell Neurosci. 2009 Jul;41(3):297-303
pubmed: 19344769