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Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis

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Item Type:Article
Title:Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis
Creators Name:Berliocchi, L. and Fava, E. and Leist, M. and Horvat, V. and Dinsdale, D. and Read, D. and Nicotera, P.
Abstract: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.
Keywords:Apoptosis, Botulinum Toxins, Cultured Cells, Cerebellum, Cytochromes c, Cytoskeleton, Electron Scanning Microscopy, Mitochondria, Nerve Tissue Proteins, Neurites, Neuroglia, Neurons, Neurotransmitter Agents, Synapses, Animals, Mice
Source:Journal of Cell Biology
ISSN:0021-9525
Publisher:Rockefeller University Press (U.S.A.)
Volume:168
Number:4
Page Range:607-618
Date:14 February 2005
Additional Information:Copyright (c) 2005 by Rockefeller University Press
Official Publication:https://doi.org/10.1083/jcb.200406126
PubMed:View item in PubMed

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