中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (7): 1290-1293.

• 原著:退行性病与再生 • 上一篇    下一篇

茉莉酮酸甲酯可调节小胶质细胞的功能

  

  • 收稿日期:2018-05-25 出版日期:2018-07-15 发布日期:2018-07-15
  • 基金资助:

    本研究得到加拿大自然科学和工程研究委员会(NSERC)和杰克布朗和家族阿尔茨海默病研究基金会的资助

Modulation of microglial functions by methyl jasmonate

Jordan A. McKenzie, Andis Klegeris   

  1. Biology Department, University of British Columbia Okanagan Campus, Kelowna, BC, Canada
  • Received:2018-05-25 Online:2018-07-15 Published:2018-07-15
  • Contact: Andis Klegeris, D.Phil.,andis.klegeris@ubc.ca.
  • Supported by:

    This study was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Jack Brown and Family Alzheimer’s Disease Research Foundation

摘要:

神经炎症可加速阿尔茨海默病(AD)的神经退行性进程,因此开发对抗中枢神经系统炎症的新型药物,是治疗和预防AD的有效途径之一。非神经元的小胶质细胞协调神经炎症反应,其不良激活与AD的发病机制有关。茉莉酮酸甲酯(MJ)已经在临床前模型中显示出抑制外周炎症的作用。最近,MJ的抗神经炎症活性在小鼠模型中得到证实,但其发挥作用的确切细胞和分子机制尚不清楚。实验假设MJ可以调节小胶质细胞功能,并试图通过两种不同的小胶质细胞体外模型来验证这一假设。结果发现,MJ抑制分化的人HL-60早幼粒细胞白血病细胞产生破坏性活性氧,而不降低其存活力;其还能选择性地上调小鼠BV-2小胶质细胞的吞噬活性,但对这些细胞的一氧化氮分泌没有影响。由于小胶质细胞吞噬作用有利于清除AD中的淀粉样蛋白β(Aβ)聚集体,因而MJ上调吞噬活性的作用以及抑制活性氧产生的效应为MJ可作为AD候选药物提供了证据。

orcid:0000-0001-6587-6458(Andis Klegeris)

 

关键词: 阿尔茨海默病, 抗炎, 神经胶质细胞, 神经炎症, 神经退行性疾病, 神经保护, 一氧化氮, 吞噬, 活性氮, 活性氧

Abstract:

Neuroinflammation contributes to the neurodegenerative processes in Alzheimer’s disease (AD); therefore, characterization of novel drug candidates aimed at combatting inflammation in the central nervous system is one of the potential avenues for the development of effective AD treatment and prevention strategies.Non-neuronal microglial cells orchestrate neuroinflammatory reactions, and their adverse activation has been linked to AD pathogenesis. Methyl jasmonate (MJ) has anti-cancer properties and has also been shown to reduce peripheral inflammation in pre-clinical models. Recently, anti-neuroinflammatory activity of MJ was demonstrated in mice, but the exact cellular and molecular mechanisms responsible for this beneficial effect are unknown. We hypothesized that MJ can regulate select microglial functions, and used two different in vitro models of microglia to test this hypothesis. MJ inhibited the production of damaging reactive oxygen species by differentiated human HL-60 promyelocytic leukemia cells without reducing their viability. MJ also selectively upregulated phagocytic activity of murine BV-2 microglia, but had no effect on nitric oxide secretion by these cells. Since microglial phagocytosis can be beneficial for clearance of amyloid β aggregates in AD, the observed upregulation of phagocytic activity by MJ, combined with its inhibitory effect on reactive oxygen species production, supports continued studies of MJ as a candidate drug for managing adverse neuroinflammation in AD.

Key words: Alzheimer’s disease, anti-inflammatory, glia, neuroinflammation, neurodegeneration, neuroprotection, nitric oxide, phagocytosis, reactive nitrogen species, reactive oxygen species