Travaglia A, La Mendola D
Center for Neural Science, New York University, New York, NY, United States.
Department of Pharmacy, University of Pisa, Pisa, Italy.
Vitam Horm. 2017;104:29-56. doi: 10.1016/bs.vh.2016.10.005. Epub 2016 Nov 29.
Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal development and survival, synaptic plasticity, and cognitive function. Dysregulation of BDNF signaling is involved in several neurodegenerative disorders, including Alzheimer's disease. Alteration of metal ion homeostasis is observed both in normal aging and in many neurodegenerative diseases. Interestingly, there is a significant overlap between brain areas characterized by metal ion dyshomeostasis and those where BDNF exerts its biological activity. Therefore, it is reasonable to speculate that metal ions, especially zinc, can modulate the activity of BDNF. The synthesis of BDNF peptidomimetic can be helpful both to understand the molecular interaction of BDNF with metal ions and to develop new drugs for neurodegenerative diseases.
脑源性神经营养因子(BDNF)是一种对神经元发育与存活、突触可塑性及认知功能至关重要的神经营养因子。BDNF信号传导失调与包括阿尔茨海默病在内的多种神经退行性疾病有关。在正常衰老过程以及许多神经退行性疾病中均观察到金属离子稳态的改变。有趣的是,以金属离子稳态失调为特征的脑区与BDNF发挥其生物活性的脑区之间存在显著重叠。因此,合理推测金属离子,尤其是锌,能够调节BDNF的活性。BDNF拟肽的合成有助于理解BDNF与金属离子的分子相互作用,并有助于开发用于神经退行性疾病的新药。