中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (3): 391-393.doi: 10.4103/1673-5374.153686

• 综述:退行性病与再生 • 上一篇    下一篇

换一种思维认识:金诺芬及右美沙芬和罗格列酮均有减少神经退行性疾病神经元丢失的可能性

  

  • 收稿日期:2015-01-30 出版日期:2015-03-20 发布日期:2015-03-20

A new look at auranofin, dextromethorphan and rosiglitazone for reduction of glia-mediated inflammation in neurodegenerative diseases

Jocelyn M. Madeira, Stephanie M. Schindler, Andis Klegeris   

  1. Department of Biology, University of British Columbia Okanagan Campus, Kelowna, British Columbia, V1V 1V7 Canada
  • Received:2015-01-30 Online:2015-03-20 Published:2015-03-20
  • Contact: Andis Klegeris, Ph.D., andis.klegeris@ubc.ca.
  • Supported by:

    This work was supported by a grant from the Jack Brown and Family Alzheimer’s Disease Research Foundation.

摘要:

包括阿尔茨海默病和帕金森病在内的许多神经退行性疾病其病理特征都有中枢神经系统慢性炎症发生,参与炎症反应的两个主要神经胶质类型是小胶质细胞和星形胶质细胞。这些细胞通常是通过提供营养物和生长因子来保护神经元的,而疾病特异性刺激能激活小胶质细胞和星形胶质细胞开始分泌神经毒性分子。据推测,减少神经胶质介导的炎症可以降低神经元缺失。非甾体类抗炎药在降低神经退行性疾病发病率上的长期使用证明了这一假说。使用非甾体类抗炎药治疗阿尔茨海默病的临床研究已经取得了不同的结果。这可能是由于非甾体类抗炎药不足以明显地减少疾病过程中的慢性神经炎症。金硫醇复合物,包括金诺芬等,在降低周围炎症方面十分有效。

Abstract:

Neurodegenerative disorders including Alzheimer’s disease are characterized by chronic inflammation in the central nervous system. The two main glial types involved in inflammatory reactions are microglia and astrocytes. While these cells normally protect neurons by providing nutrients and growth factors, disease specific stimuli can induce glial secretion of neurotoxins. It has been hypothesized that reducing glia-mediated inflammation could diminish neuronal loss. This hypothesis is supported by observations that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is linked with lower incidences of neurodegenerative disease. It is possible that the NSAIDs are not potent enough to appreciably reduce chronic neuroinflammation after disease processes are fully established. Gold thiol compounds, including auranofin, comprise another class of medications effective at reducing peripheral inflammation. We have demonstrated that auranofin inhibits human microglia- and astrocyte-mediated neurotoxicity. Other drugs which are currently used to treat peripheral inflammatory conditions could be helpful in neurodegenerative disease. Three different classes of anti-inflammatory compounds, which have a potential to inhibit neuroinflammation are highlighted below.

Key words: dextromethorphan, rosiglitazone, Alzheimer’s disease, neuroinflammationv neurodegeneration, microglia, astrocytes