Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis.
Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis.
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DOI：
10.1083/jcb.200406126
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发表时间：
2005-02-14
期刊：
影响因子：
--
通讯作者：
Nicotera P
中科院分区：
文献类型：
--
作者：
Berliocchi L;Fava E;Leist M;Horvat V;Dinsdale D;Read D;Nicotera P
梭菌神经毒素是细菌内肽酶，可裂解外周运动神经元中的主要 SNARE 蛋白。在这里，我们发现肉毒杆菌神经毒素 C1 (BoNT/C) 对中枢神经系统神经元中突触结构的破坏会激活轴突树突网络和细胞体中不同的神经退行性程序。神经突在早期通过活性半胱天冬酶依赖性断裂而退化，其特征是能量活性线粒体的分离。随后，细胞体线粒体释放细胞色素c，随后发生半胱天冬酶激活、凋亡核浓缩、膜电位丧失，最后细胞肿胀和裂解。神经胶质细胞对死亡过程的识别和清除也先于凋亡细胞体的去除，这与不同退化过程的时间和空间隔离一致。我们的结果表明，为了应对广泛的突触损伤，神经元首先拆除它们的连接，最后当它们的空间关系丢失时发生细胞凋亡。
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.
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影响因子：
4.7
作者：
BAGETTA, G;CORASANITI, MT;BOWERY, NG
通讯作者：
BOWERY, NG
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
16.2
作者：
ANKARCRONA, M;DYPBUKT, JM;NICOTERA, P
通讯作者：
NICOTERA, P
影响因子：
5.3
作者：
Dickson, TC;King, CE;Vickers, JC
通讯作者：
Vickers, JC
DOI：
10.1097/00005072-199906000-00008
发表时间：
1999-06-01
影响因子：
3.2
作者：
Hatanpää, K;Isaacs, KR;Rapoport, SI
通讯作者：
Rapoport, SI