日本千葉大學(xué)研究人員日前發(fā)表報(bào)告說,,他們發(fā)現(xiàn)一種名為米諾環(huán)素的抗生素具有促進(jìn)神經(jīng)細(xì)胞生長(zhǎng)的功能,。這一發(fā)現(xiàn)將有助于修復(fù)因疾病,、中毒等導(dǎo)致的神經(jīng)損傷,。
米諾環(huán)素屬于四環(huán)素類廣譜抗生素。研究人員之前給因興奮劑中毒而導(dǎo)致神經(jīng)細(xì)胞受損的猴子使用米諾環(huán)素,,成功令猴子的神經(jīng)恢復(fù)了功能,。在本次研究中,他們致力于深入分析米諾環(huán)素促進(jìn)神經(jīng)細(xì)胞生長(zhǎng)的機(jī)理,。
研究人員在試管中培養(yǎng)大鼠的神經(jīng)祖細(xì)胞(神經(jīng)細(xì)胞發(fā)育完成前的前體細(xì)胞),,然后向試管內(nèi)添加米諾環(huán)素。結(jié)果發(fā)現(xiàn),,米諾環(huán)素可促使神經(jīng)祖細(xì)胞中一種特殊分子的數(shù)量不斷增加,,進(jìn)而令神經(jīng)細(xì)胞數(shù)量增加。這種分子的功能是啟動(dòng)復(fù)制基因信息的蛋白質(zhì)的合成進(jìn)程,,這對(duì)神經(jīng)細(xì)胞發(fā)育至關(guān)重要,。
這項(xiàng)成果已發(fā)表在新一期美國(guó)《科學(xué)公共圖書館綜合卷》上。(生物谷Bioon.com)
生物谷推薦英文摘要:
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.