The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease
The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease
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DOI：
10.1006/mcne.2001.1016
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发表时间：
2001-08-01
影响因子：
3.5
通讯作者：
Coughlin, MD
中科院分区：
文献类型：
--
作者：
Fahnestock, M;Michalski, B;Coughlin, MD
神经生长因子(NGF)对周围和中枢神经系统神经元(包括阿尔茨海默病(AD)中变性的基底前脑胆碱能神经元(BFCN))的调节、分化和生存具有重要作用。成熟的NGF蛋白是由更大的前体ProNGF加工而成的。我们证明，在小鼠、大鼠和人脑组织中，proNGF是NGF的主要形式，而很少或没有检测到成熟的NGF。先前的报告显示，通过酶联免疫吸附测定，NGF蛋白在AD BFCN靶区如海马区和皮质区增加。利用Western blotting，我们证明了AD顶叶皮质中proNGF的表达是对照组的两倍，这表明正是这种前体形式proNGF在AD中积累。这种增加可能反映了生物学活性的proNGF的作用，或者是翻译后干扰在NGF生物合成中减少了proNGF在AD中向成熟NGF的加工。
Nerve growth factor (NGF) is important for regulation, differentiation, and survival of peripheral and central nervous system neurons, including basal forebrain cholinergic neurons (BFCN) which degenerate in Alzheimer's disease (AD). Mature NGF protein is processed from a larger precursor, proNGF. We demonstrate that proNGF is the predominant form of NGF in mouse, rat, and human brain tissue, whereas little or no mature NGF is detected. Previous reports showed NGF protein, measured by ELISA, is increased in AD BFCN target regions such as hippocampus and cortex. Using Western blotting, we demonstrate a twofold increase in proNGF in AD parietal cortex compared to controls, indicating that it is this precursor form, proNGF, that accumulates in AD. This increase may reflect either a role for biologically active proNGF or posttranslational disturbances in NGF biosynthesis that decrease the processing of proNGF to mature NGF in AD.