Abstract

Neurotrophic factors, now termed neurotrophins, which belong to a class of polypeptidyl agents, have been shown to potentially be beneficial for the treatment of neurodegenerative diseases such as Alzheimer’s disease, because endogenous neurotrophic factors (NGF, BDNF, NT3, NT4) have been recognized to play critical roles in the promotion of neurogenesis, differentiation, and neuroprotection throughout the development of the central nervous system. However, high-molecular weight proteins are unable to cross the blood–brain barrier and are easily decomposed by peptidase under physiological conditions. To address this issue, small molecules that can mimic the functions of neurotrophic factors would be promising alternatives for the treatment of neurodegenerative disease. We have continued to search for natural products having typical neurotrophic properties, which can cause neurogenesis, enhance neurite outgrowth, and protect neuronal death using three cellular systems (PC12, rat cortical neurons, and MEB5 cells). In this review, we summarize the neurotrophic activities and synthesis of dimeric isocuparane-type sesquiterpenes from the liverwort, Mastigophora diclados, the mechanism of neurotrophic neolignans, magnolol, honokiol and their sesquiterpene derivatives, and introduce unique neurotrophin-mimic natural products, including seco-prezizaane-type sesquiterpenes from the Illicium species, vibsane-type diterpenes from Viburnum awabuki, and miscellaneous natural products with neurotrophic effects discovered by us.

Graphic abstract

中文翻译：

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寻找神经营养性天然产物及其化学和机理。

摘要

由于已经认识到内源性神经营养因子（NGF，BDNF，NT3，NT4），现已证明神经营养因子（现在称为神经营养蛋白）属于一类多肽类药物，对神经退行性疾病（例如阿尔茨海默氏病）具有潜在的治疗作用在整个中枢神经系统发育过程中，在促进神经发生，分化和神经保护方面起关键作用。但是，高分子量蛋白质无法穿过血脑屏障，在生理条件下很容易被肽酶分解。为了解决这个问题，可以模拟神经营养因子功能的小分子将成为治疗神经退行性疾病的有前途的替代方法。我们一直在使用三种细胞系统（PC12，大鼠皮层神经元和MEB5细胞）寻找具有典型神经营养特性的天然产物，这些产物可以引起神经发生，增强神经突向外生长并保护神经元死亡。在这篇综述中，我们总结了来自地艾的神经营养活性和二聚异iso烷型倍半萜的合成，鞭毛纲diclados，神经营养新木脂体，厚朴，厚朴的机理及其倍半萜烯衍生物，并引入独特的神经营养因子模拟天然产品，包括山高从-prezizaane型倍半萜八角物种，从vibsane型双萜琼花日本珊瑚树，杂天然产物与我们发现的神经营养作用有关。

图形摘要