Microglia-inhibiting activity of Parkinson's disease drug amantadine

被引：48

作者：

Kim, Jong-Heon ^{[1
,2
]}

Lee, Ho-Won ^{[2
,3
]}

Hwang, Jaegyu ^{[1
,2
]}

Kim, Jaehong ^{[1
,2
]}

Lee, Min-Jeong ^{[2
,4
]}

Han, Hyung-Soo ^{[2
,4
]}

Lee, Won-Ha ^{[5
]}

Suk, Kyoungho ^{[1
,2
]}

机构：

[1] Kyungpook Natl Univ, Dept Pharmacol, Sch Med, Taegu 700422, South Korea

[2] Kyungpook Natl Univ, CMRI, Sch Med, Brain Sci & Engn Inst, Taegu 700422, South Korea

[3] Kyungpook Natl Univ, Dept Neurol, Sch Med, Taegu 700422, South Korea

[4] Kyungpook Natl Univ, Dept Physiol, Sch Med, Taegu 700422, South Korea

[5] Kyungpook Natl Univ, Dept Genet Engn, Sch Life Sci & Biotechnol, Taegu 700422, South Korea

来源：

NEUROBIOLOGY OF AGING | 2012年 / 33卷 / 09期

关键词：

Amantadine; Microglia; Neuroinflammation; Parkinson's disease; FORCED SWIMMING TEST; RAT-BRAIN; 1-ADAMANTANAMINE AMANTADINE; INFLAMMATORY ACTIVATION; ANTIVIRAL ACTIVITY; NEUROINFLAMMATION; INFLUENZA; MEMANTINE; NEURONS; NEURODEGENERATION;

D O I：

10.1016/j.neurobiolaging.2011.08.011

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Amantadine is currently used as an antiviral and an antiparkinsonian drug. Although the drug is known to bind a viral proton channel protein, the mechanism of action in Parkinson's disease (PD) remains to be determined. This study investigated whether the drug has an inhibitory effect on microglial activation and neuroinflammation, which have been implicated in the progression of neurodegenerative processes. Using cultured microglial cells, it was demonstrated that the drug inhibited inflammatory activation of microglia and a signaling pathway that governs the microglial activation. The drug reduced the expression and production of proinflammatory mediators in bacterial lipopolysaccharide-stimulated microglia cells. The microglia-inhibiting activity of amantadine was also demonstrated in a microglia/neuron coculture and animal models of neuroinflammation and Parkinson's disease. Collectively, our results suggest that amantadine may act on microglia in the central nervous system to inhibit their inflammatory activation, thereby attenuating neuroinflammation. These results provide a molecular basis of the glia-targeted mechanism of action for amantadine. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：2145 / 2159

页数：15

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