Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease
Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease
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DOI：
10.1016/s0169-328x(03)00003-2
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发表时间：
2003-03-17
期刊：
影响因子：
--
通讯作者：
Fahnestock, M
中科院分区：
文献类型：
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作者：
Michalski, B;Fahnestock, M
脑源性神经营养因子（BDNF）促进阿尔茨海默病中受影响的主要神经元类型的功能和存活，如海马、皮质和基底前脑胆碱能神经元。我们和其他人已经证明了阿尔茨海默病海马和皮层中BDNF mRNA表达的减少，这可能有助于解释这些神经元的选择性脆弱性。几项研究也表明阿尔茨海默病中BDNF蛋白的减少。BDNF蛋白作为前体proBDNF合成，其被切割成成熟的14-kDa形式。我们在这里证明，BDNF存在的proBDNF和成熟的BDNF的混合物中的所有区域的人脑测试。使用蛋白质印迹法，我们观察到与对照组相比，阿尔茨海默病顶叶皮层中的proBDNF水平降低了40%。因此，通过ELISA和免疫组织化学测量的BDNF蛋白的减少可能代表两种BDNF形式的混合物，并且先前报道的BDNF蛋白的减少可能是由于，至少部分是由于proBDNF水平的显著降低。虽然proBDNF的生物活性是未知的，减少proBDNF可能有功能的后果，选择性神经元变性在阿尔茨海默氏病的大脑。(C)2003 Elsevier Science B. V.保留所有权利。
Brain-derived neurotrophic factor (BDNF) promotes the function and survival of the major neuronal types affected in Alzheimer disease, such as hippocampal, cortical and basal forebrain cholinergic neurons. We and others have demonstrated a reduction in BDNF mRNA expression in Alzheimer's disease hippocampus and cortex, which may help to explain the selective vulnerability of these neurons. Several studies have also shown decreased BDNF protein in Alzheimer's disease. BDNF protein is synthesized as a precursor, proBDNF, which is cleaved to the mature 14-kDa form. We demonstrate here that BDNF exists as a mixture of proBDNF and mature BDNF in all regions tested of human brain. Using Western blotting, we observe a 40% reduction in proBDNF levels in Alzheimer's disease parietal cortex compared to controls. Thus, decreased BDNF protein measured by ELISA and immunohistochemistry likely represents a mixture of the two BDNF forms, and previously reported decreases in BDNF protein may be due, at least in part, to a significant reduction in proBDNF levels. Although the biological activity of proBDNF is unknown, reduced proBDNF may have functional consequences for the selective neuronal degeneration in Alzheimer's disease brain. (C) 2003 Elsevier Science B.V. All rights reserved.