Fahnestock M, Michalski B, Xu B, Coughlin M D
Department of Pyschiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Mol Cell Neurosci. 2001 Aug;18(2):210-20. doi: 10.1006/mcne.2001.1016.
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.
神经生长因子（NGF）对于外周和中枢神经系统神经元的调节、分化及存活至关重要，包括在阿尔茨海默病（AD）中会发生退化的基底前脑胆碱能神经元（BFCN）。成熟的NGF蛋白是由一种更大的前体——前体神经生长因子（proNGF）加工而来。我们证明，proNGF是小鼠、大鼠和人类脑组织中NGF的主要形式，而成熟NGF的检测量很少或未检测到。先前的报告显示，通过酶联免疫吸附测定（ELISA）测得的NGF蛋白在AD的BFCN靶区域如海马体和皮质中有所增加。使用蛋白质印迹法，我们证明与对照组相比，AD顶叶皮质中的proNGF增加了两倍，这表明在AD中积累的正是这种前体形式的proNGF。这种增加可能反映了具有生物活性的proNGF的作用，或者是NGF生物合成中的翻译后干扰，从而减少了AD中proNGF向成熟NGF的加工。
