Department of Human Physiology, Flinders University, Adelaide, SA, Australia.
Neurotox Res. 2010 Apr;17(3):257-67. doi: 10.1007/s12640-009-9098-x. Epub 2009 Aug 13.
Alzheimer's disease (AD) is characterized pathologically by the deposition of amyloid-beta peptides (Abeta), neurofibrillary tangles, distinctive neuronal loss and neurite dystrophy. Nerve growth factor (NGF) has been suggested to be involved in the pathogenesis of AD, however, the role of its precursor (proNGF) in AD remains unknown. In this study, we investigated the effect of proNGF on neuron death, neurite growth and Abeta production, in vitro and in vivo. We found that proNGF promotes the death of different cell lines and primary neurons in culture, likely dependent on the expression of p75(NTR). We for the first time found that proNGF has an opposite role in neurite growth to that of mature NGF, retarding neurite growth in both cell lines and primary neurons. proNGF is localized to the Abeta plaques in AD mice brain, however, it had no significant effect on Abeta production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.
阿尔茨海默病（AD）的病理学特征是淀粉样β肽（Abeta）的沉积、神经原纤维缠结、明显的神经元丧失和神经突营养不良。神经生长因子（NGF）被认为与 AD 的发病机制有关，然而，其前体（proNGF）在 AD 中的作用尚不清楚。在这项研究中，我们研究了 proNGF 在体外和体内对神经元死亡、神经突生长和 Abeta 产生的影响。我们发现 proNGF 可能依赖于 p75（NTR）的表达，促进不同细胞系和原代神经元的死亡。我们首次发现 proNGF 在神经突生长方面与成熟的 NGF 作用相反，抑制细胞系和原代神经元的神经突生长。proNGF 定位于 AD 小鼠大脑中的 Abeta 斑块中，但对体外和体内的 Abeta 产生没有显著影响。我们的研究结果表明，proNGF 是参与 AD 发病机制的重要因素。
