On the molecular basis linking Nerve Growth Factor (NGF) to Alzheimer's disease
On the molecular basis linking Nerve Growth Factor (NGF) to Alzheimer's disease
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DOI：
10.1007/s10571-006-9112-2
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发表时间：
2006-07-01
影响因子：
4
通讯作者：
Cattaneo, Antonino
中科院分区：
文献类型：
--
作者：
Capsoni, Simona;Cattaneo, Antonino
1. 阿尔茨海默病（AD）在病理学上由淀粉样肽沉积和神经原纤维缠结所定义，其特征是由于皮质胆碱能显著耗竭而导致认知和记忆功能进行性丧失。
2. 皮质的胆碱能神经支配由基底前脑胆碱能神经元提供。神经营养因子神经生长因子（NGF）促进基底前脑胆碱能神经元的存活和分化。
3. 这一论断是过去20年所提出的假说的基础，即NGF缺乏将是散发性阿尔茨海默病病因中涉及的因素之一。
4. 在这篇综述中，我们将总结基于表达中和NGF的转基因抗体而产生和鉴定阿尔茨海默病小鼠模型（AD11抗 - NGF小鼠）的数据。将根据近期把NGF及其前体pro - NGF重新置于阿尔茨海默病样神经退行性变研究阶段的相关研究来讨论AD11小鼠的阿尔茨海默病样表型，这些研究表明前体pro - NGF参与了导致阿尔茨海默病神经退行性变的级联反应之一。
1. Alzheimer's disease (AD) is pathologically defined by the deposition of amyloid peptide and neurofibrillary tangles and is characterized by a progressive loss of cognition and memory function, due to marked cortical cholinergic depletion.2. Cholinergic cortical innervation is provided by basal forebrain cholinergic neurons. The neurotrophin Nerve Growth Factor (NGF) promotes survival and differentiation of basal forebrain cholinergic neurons.3. This assertion has been at the basis of the hypothesis developed in the last 20 years, whereby NGF deprivation would be one of the factor involved in the etiology of sporadic forms of AD.4. In this review, we shall summarize data that lead to the production and characterization of a mouse model for AD (AD11 anti-NGF mice), based on the expression of transgenic antibodies neutralizing NGF. The AD-like phenotype of AD11 mice will be discussed on the basis of recent studies that have posed NGF and its precursor pro-NGF back to the stage of AD-like neurodegeneration, showing the involvement of the precursor pro-NGF in one of the cascades leading to AD neurodegeneration.