PLoS ONE:米诺环素可促进神经细胞生长

2010-11-23 00:00 · Elliot

日本千叶大学研究人员日前发表报告说,他们发现一种名为米诺环素的抗生素具有促进神经细胞生长的功能。这一发现将有助于修复因疾病、中毒等导致的神经损伤。 米诺环素属于四环素类广谱抗生素。研究人员之前给因兴奋剂中毒而导致神经细胞受损的猴子使用米诺环素,成功令猴子的神经恢复了功能。在本次

日本千叶大学研究人员日前发表报告说,他们发现一种名为米诺环素的抗生素具有促进神经细胞生长的功能。这一发现将有助于修复因疾病、中毒等导致的神经损伤。

米诺环素属于四环素类广谱抗生素。研究人员之前给因兴奋剂中毒而导致神经细胞受损的猴子使用米诺环素,成功令猴子的神经恢复了功能。在本次研究中,他们致力于深入分析米诺环素促进神经细胞生长的机理。

研究人员在试管中培养大鼠的神经祖细胞(神经细胞发育完成前的前体细胞),然后向试管内添加米诺环素。结果发现,米诺环素可促使神经祖细胞中一种特殊分子的数量不断增加,进而令神经细胞数量增加。这种分子的功能是启动复制基因信息的蛋白质的合成进程,这对神经细胞发育至关重要。

这项成果已发表在新一期美国《科学公共图书馆综合卷》上。

 

推荐英文摘要:

PLoS ONE 5(11): e15430. doi:10.1371/journal.pone.0015430

A Novel Target of Action of Minocycline in NGF-Induced Neurite Outgrowth in PC12 Cells: Translation Initiator Factor eIF4AI

Kenji Hashimoto*, Tamaki Ishima

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan

Background

Minocycline, a second-generation tetracycline antibiotic, has potential activity for the treatment of several neurodegenerative and psychiatric disorders. However, its mechanisms of action remain to be determined.

Methodology/Principal Findings

We found that minocycline, but not tetracycline, significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration dependent manner. Furthermore, we found that the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP3) receptors and several common signaling molecules (PLC-γ, PI3K, Akt, p38 MAPK, c-Jun N-terminal kinase (JNK), mammalian target of rapamycin (mTOR), and Ras/Raf/ERK/MAPK pathways) might be involved in the active mechanism of minocycline. Moreover, we found that a marked increase of the eukaryotic translation initiation factor eIF4AI protein by minocycline, but not tetracycline, might be involved in the active mechanism for NGF-induced neurite outgrowth.

Conclusions/Significance

These findings suggest that eIF4AI might play a role in the novel mechanism of minocycline. Therefore, agents that can increase eIF4AI protein would be novel therapeutic drugs for certain neurodegenerative and psychiatric diseases.

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