Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.
Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.
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DOI：
10.1371/journal.pone.0013337
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发表时间：
2010-10-13
期刊：
影响因子：
3.7
通讯作者：
Delalle I
中科院分区：
文献类型：
--
作者：
Kao PF;Davis DA;Banigan MG;Vanderburg CR;Seshadri S;Delalle I
在阿尔茨海默病（AD）的发展过程中，海马神经元经历细胞骨架重组，导致退行性和再生性变化。随着神经元缠结的形成和营养不良的神经突的出现，出现了具有生长锥的萌芽神经元突起。肌动蛋白和微管蛋白对于正常的神经突发育和对损伤和神经退行性刺激的再生反应是不可缺少的。我们以前已经表明，肌动蛋白帽蛋白β 2亚基，Capzb 2，结合微管蛋白，并在tau蛋白的存在下，影响微管聚合所需的轴突生长和正常的生长锥形态。因此，海马神经元中的Capzb 2沉默导致短的营养不良性神经突，在包括AD的神经退行性疾病中可见。在这里，我们证明了统计学上显着增加的Capzb 2表达的人在中期，Braak和Braak阶段（BB）III-IV，非家族性AD相比，对照组中的尸体后campi。Capzb 2在进行性AD阶段表达的动力学不能归因于反应性星形胶质细胞增多。此外，AD BB III-IV中CA 1锥体神经元中Capzb 2 mRNA表达的增加伴随着海马神经元中突触可塑性介质脑源性神经营养因子（BDNF）受体酪氨酸激酶B（Trk B）mRNA表达的增加。因此，Capzb 2和TrkB的上调可能反映了在AD进展的特定阶段海马CA 1神经元中发生的细胞骨架重组和/或再生反应。
During the progression of Alzheimer's disease (AD), hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB) III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF) receptor tyrosine kinase B (TrkB), mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression.
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影响因子：
9.8
作者：
Davis, David A.;Wilson, Meredith H.;Delalle, Ivana
通讯作者：
Delalle, Ivana
影响因子：
39.2
作者：
Larson, EB;Wang, L;Kukull, W
通讯作者：
Kukull, W
DOI：
10.1023/b:neur.0000021903.24849.6c
发表时间：
2003-11-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Avwenagha, O;Campbell, G;Bird, MM
通讯作者：
Bird, MM
DOI：
10.1016/s0169-328x(97)00125-3
发表时间：
1997-10-03
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Connor, B;Young, D;Dragunow, M
通讯作者：
Dragunow, M
影响因子：
6.2
作者：
BEACH, TG;WALKER, R;MCGEER, EG
通讯作者：
MCGEER, EG