Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HC(C)/A)

Botulinum neurotoxins (BoNTs) are extremely potent naturally occurring poisons that act by silencing neurotransmission. Intriguingly, in addition to preventing presynaptic vesicle fusion, BoNT serotype A (BoNT/A) can also promote axonal regeneration in preclinical models. Here we report that the non...

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Detalles Bibliográficos
Autores principales: Solabre Valois, Luis, Shi, Vanilla (Hua), Bishop, Paul, Zhu, Bangfu, Nakamura, Yasuko, Wilkinson, Kevin A., Henley, Jeremy M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Short Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143998/
https://www.ncbi.nlm.nih.gov/pubmed/34041508
http://dx.doi.org/10.1016/j.ibneur.2021.04.002
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author Solabre Valois, Luis
Shi, Vanilla (Hua)
Bishop, Paul
Zhu, Bangfu
Nakamura, Yasuko
Wilkinson, Kevin A.
Henley, Jeremy M.
author_facet Solabre Valois, Luis
Shi, Vanilla (Hua)
Bishop, Paul
Zhu, Bangfu
Nakamura, Yasuko
Wilkinson, Kevin A.
Henley, Jeremy M.
author_sort Solabre Valois, Luis
collection PubMed
description Botulinum neurotoxins (BoNTs) are extremely potent naturally occurring poisons that act by silencing neurotransmission. Intriguingly, in addition to preventing presynaptic vesicle fusion, BoNT serotype A (BoNT/A) can also promote axonal regeneration in preclinical models. Here we report that the non-toxic C-terminal region of the receptor-binding domain of heavy chain BoNT/A (HC(C)/A) activates the small GTPase Rac1 and ERK pathway to potentiate axonal outgrowth, dendritic protrusion formation and synaptic vesicle release in hippocampal neurons. These data are consistent with HC(C)/A exerting neurotrophic properties, at least in part, independent of any BoNT catalytic activity or toxic effect.
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spelling pubmed-81439982021-05-25 Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HC(C)/A) Solabre Valois, Luis Shi, Vanilla (Hua) Bishop, Paul Zhu, Bangfu Nakamura, Yasuko Wilkinson, Kevin A. Henley, Jeremy M. IBRO Neurosci Rep Short Communication Botulinum neurotoxins (BoNTs) are extremely potent naturally occurring poisons that act by silencing neurotransmission. Intriguingly, in addition to preventing presynaptic vesicle fusion, BoNT serotype A (BoNT/A) can also promote axonal regeneration in preclinical models. Here we report that the non-toxic C-terminal region of the receptor-binding domain of heavy chain BoNT/A (HC(C)/A) activates the small GTPase Rac1 and ERK pathway to potentiate axonal outgrowth, dendritic protrusion formation and synaptic vesicle release in hippocampal neurons. These data are consistent with HC(C)/A exerting neurotrophic properties, at least in part, independent of any BoNT catalytic activity or toxic effect. Elsevier 2021-05-13 /pmc/articles/PMC8143998/ /pubmed/34041508 http://dx.doi.org/10.1016/j.ibneur.2021.04.002 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Short Communication
Solabre Valois, Luis
Shi, Vanilla (Hua)
Bishop, Paul
Zhu, Bangfu
Nakamura, Yasuko
Wilkinson, Kevin A.
Henley, Jeremy M.
Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HC(C)/A)
title Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HC(C)/A)
title_full Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HC(C)/A)
title_fullStr Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HC(C)/A)
title_full_unstemmed Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HC(C)/A)
title_short Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HC(C)/A)
title_sort neurotrophic effects of botulinum neurotoxin type a in hippocampal neurons involve activation of rac1 by the non-catalytic heavy chain (hc(c)/a)
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143998/
https://www.ncbi.nlm.nih.gov/pubmed/34041508
http://dx.doi.org/10.1016/j.ibneur.2021.04.002
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