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Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis
Clostridial neurotoxins are bacterial endopeptidases that cleave the major SNARE proteins in peripheral motorneurons. Here, we show that disruption of synaptic architecture by botulinum neurotoxin C1 (BoNT/C) in central nervous system neurons activates distinct neurodegenerative programs in the axo-...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171755/ https://www.ncbi.nlm.nih.gov/pubmed/15716378 http://dx.doi.org/10.1083/jcb.200406126 |
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author | Berliocchi, Laura Fava, Eugenio Leist, Marcel Horvat, Volker Dinsdale, David Read, David Nicotera, Pierluigi |
author_facet | Berliocchi, Laura Fava, Eugenio Leist, Marcel Horvat, Volker Dinsdale, David Read, David Nicotera, Pierluigi |
author_sort | Berliocchi, Laura |
collection | PubMed |
description | Clostridial neurotoxins are bacterial endopeptidases that cleave the major SNARE proteins in peripheral motorneurons. Here, we show that disruption of synaptic architecture by botulinum neurotoxin C1 (BoNT/C) in central nervous system neurons activates distinct neurodegenerative programs in the axo-dendritic network and in the cell bodies. Neurites degenerate at an early stage by an active caspase-independent fragmentation characterized by segregation of energy competent mitochondria. Later, the cell body mitochondria release cytochrome c, which is followed by caspase activation, apoptotic nuclear condensation, loss of membrane potential, and, finally, cell swelling and lysis. Recognition and scavenging of dying processes by glia also precede the removal of apoptotic cell bodies, in line with a temporal and spatial segregation of different degenerative processes. Our results suggest that, in response to widespread synaptic damage, neurons first dismantle their connections and finally undergo apoptosis, when their spatial relationships are lost. |
format | Text |
id | pubmed-2171755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21717552008-03-05 Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis Berliocchi, Laura Fava, Eugenio Leist, Marcel Horvat, Volker Dinsdale, David Read, David Nicotera, Pierluigi J Cell Biol Research Articles Clostridial neurotoxins are bacterial endopeptidases that cleave the major SNARE proteins in peripheral motorneurons. Here, we show that disruption of synaptic architecture by botulinum neurotoxin C1 (BoNT/C) in central nervous system neurons activates distinct neurodegenerative programs in the axo-dendritic network and in the cell bodies. Neurites degenerate at an early stage by an active caspase-independent fragmentation characterized by segregation of energy competent mitochondria. Later, the cell body mitochondria release cytochrome c, which is followed by caspase activation, apoptotic nuclear condensation, loss of membrane potential, and, finally, cell swelling and lysis. Recognition and scavenging of dying processes by glia also precede the removal of apoptotic cell bodies, in line with a temporal and spatial segregation of different degenerative processes. Our results suggest that, in response to widespread synaptic damage, neurons first dismantle their connections and finally undergo apoptosis, when their spatial relationships are lost. The Rockefeller University Press 2005-02-14 /pmc/articles/PMC2171755/ /pubmed/15716378 http://dx.doi.org/10.1083/jcb.200406126 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Berliocchi, Laura Fava, Eugenio Leist, Marcel Horvat, Volker Dinsdale, David Read, David Nicotera, Pierluigi Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis |
title | Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis |
title_full | Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis |
title_fullStr | Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis |
title_full_unstemmed | Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis |
title_short | Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis |
title_sort | botulinum neurotoxin c initiates two different programs for neurite degeneration and neuronal apoptosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171755/ https://www.ncbi.nlm.nih.gov/pubmed/15716378 http://dx.doi.org/10.1083/jcb.200406126 |
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