Memantine prolongs survival in an amyotrophic lateral sclerosis mouse model.
Memantine prolongs survival in an amyotrophic lateral sclerosis mouse model.
复制标题
美金刚可延长肌萎缩侧索硬化症小鼠模型的生存期。
DOI：
10.1111/j.1460-9568.2005.04431.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Zhang,Dongxian
中科院分区：
文献类型：
--
作者：
Wang,Rengang;Zhang,Dongxian
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which results from selective loss of upper and lower motor neurons. Mouse models of ALS, such as one carrying the G93A mutant of the human Cu‐Zn superoxide dismutase gene[SOD1(G93A)], develop motor neuron pathology and clinical symptoms similar to those observed in ALS patients. There is compelling evidence that both direct and indirect glutamate toxicity contribute to the pathogenesis of motor neuron degeneration. However, the therapeutic effect of various glutamate receptor antagonists has not been clearly demonstrated. Memantine is a noncompetitiveN‐methyl‐d‐aspartate (NMDA) receptor antagonist. It has been shown to protect neurons against NMDA‐ or glutamate‐induced toxicityin vitroand in animal models of neurodegenerative diseases. In the current study, we have examined the therapeutic efficacy of memantine in an ALS mouse model carrying a high copy number of SOD1(G93A). Memantine treatment significantly delayed the disease progression and increased the life span of SOD1(G93A) mice, from 121.4 ± 5.5 to 129.7 ± 4.5 days (P= 0.032). Furthermore, NMDA receptor subunits were reliably detected in the spinal cord of SOD1(G93A) mice and their expression levels were similar to those in the wild‐type littermate control. Therefore, the neuroprotective effect of memantine in SOD1(G93A) mice is most probably due to the inhibition of spinal cord NMDA receptors. In view of the long‐term usage of memantine for dementia patients, with excellent tolerance and safety, these data suggest that memantine may be used in ALS patients alone or in combination with other therapies to prolong survival.
