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粘细菌天然产物:神经紊乱药物发现中被低估的产物来源。

Myxobacterial natural products: An under-valued source of products for drug discovery for neurological disorders.

机构信息

Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran; Neuropharmacology Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia.

Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.

出版信息

Neurotoxicology. 2018 May;66:195-203. doi: 10.1016/j.neuro.2018.02.017. Epub 2018 Mar 2.

Abstract

Age-related disorders impose noticeable financial and emotional burdens on society. This impact is becoming more prevalent with the increasing incidence of neurodegenerative diseases and is causing critical concerns for treatment of patients worldwide. Parkinson's disease, Alzheimer's disease, multiple sclerosis and motor neuron disease are the most prevalent and the most expensive to treat neurodegenerative diseases globally. Therefore, exploring effective therapies to overcome these disorders is a necessity. Natural products and their derivatives have increasingly attracted attention in drug discovery programs that have identified microorganisms which produce a large range of metabolites with bioactive properties. Myxobacteria, a group of Gram-negative bacteria with large genome size, produce a wide range of secondary metabolites with significant chemical structures and a variety of biological effects. They are potent natural product producers. In this review paper, we attempt to overview some secondary metabolites synthesized by myxobacteria with neuroprotective activity through known mechanisms including production of polyunsaturated fatty acids, reduction of apoptosis, immunomodulation, stress reduction of endoplasmic reticulum, stabilization of microtubules, enzyme inhibition and serotonin receptor modulation.

摘要

年龄相关性疾病给社会带来了显著的经济和情感负担。随着神经退行性疾病发病率的增加,这种影响越来越普遍,这对全球患者的治疗提出了严峻的挑战。帕金森病、阿尔茨海默病、多发性硬化症和运动神经元病是全球最常见和治疗费用最高的神经退行性疾病。因此,探索有效的治疗方法来克服这些疾病是必要的。天然产物及其衍生物在药物发现计划中越来越受到关注,这些计划已经发现了能够产生具有生物活性的大量代谢产物的微生物。粘细菌是一类革兰氏阴性细菌,具有较大的基因组大小,能够产生广泛的具有显著化学结构和多种生物效应的次级代谢产物。它们是强有力的天然产物生产者。在这篇综述文章中,我们试图概述通过已知机制(包括产生多不饱和脂肪酸、减少细胞凋亡、免疫调节、减轻内质网应激、稳定微管、抑制酶活性和调节 5-羟色胺受体)合成具有神经保护活性的粘细菌次级代谢产物。

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