生物谷專題匯總：神經(jīng)再生與修復(fù)
美國波士頓兒童醫(yī)院的研究人員發(fā)現(xiàn)一種叫Mst3b的酶，在損壞軸突（神經(jīng)纖維）的修復(fù)再生過程中是必需的,，而且該酶對活體動物模型的中樞和周邊神經(jīng)系統(tǒng)都是有效的。
這項研究結(jié)果發(fā)布在10月25日Nature Neuroscience的在線版本上,。研究表明，Mst3b或其激動劑可能是治療中風(fēng),，脊髓破壞和大腦受傷的一種方式,。通常情況下，中樞神經(jīng)系統(tǒng)中的神經(jīng)元不能再生受損的神經(jīng)纖維,，這大大限制了人類大腦或脊髓受傷的恢復(fù),。
這項研究是由Nina Irwin和Larry Benowitz博士主持的，是在先前基礎(chǔ)上進行的,。在2002年,，他們發(fā)現(xiàn)了一種小分子inosine，能夠刺激軸突再生,，隨后的研究表明其能修復(fù)受傷動物的神經(jīng)學(xué)功能,。2006年，Benowitz和他的同事發(fā)現(xiàn)一個先前未知的生長因子oncomodulin,，其能夠顯著影響軸突發(fā)育,。在深入研究了inosine和oncomodulin的作用機理后，研究人員發(fā)現(xiàn)這兩種化合物都激活了酶Mst3b,，該酶可能是控制軸突生長的細胞信號通路的精密調(diào)節(jié)器,。Mst3b，是一種蛋白激酶,，能依次激活信號使得軸突生長必需的基因得以表達,。
在視神經(jīng)破壞的老鼠中，研究人員發(fā)現(xiàn)Mst3b缺失后,，軸突幾乎沒有再生,，即使暴露在一些能夠增強軸突生長的因子中。在細胞培養(yǎng)中,，當激活的Mst3b在神經(jīng)元中表達的時候，軸突生長增加,。
研究人員測試了與Mst3b相關(guān)的所有生長因子,，ncomodulin,inosine, 腦導(dǎo)神經(jīng)營養(yǎng)因子（brain-derived neurotropic factor），神經(jīng)生長因子,。事實上,，激活Mst3b本身就已經(jīng)足夠使軸突生長即使沒有生長因子,。就對神經(jīng)細胞的理解而言，這項發(fā)現(xiàn)也已經(jīng)是很讓人興奮的了,。Benowitz介紹說,。
接下來研究人員將關(guān)注Mst3b刺激神經(jīng)纖維生長的機制，或能為大腦或脊髓受傷開辟新的治療手段,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Neuroscience 12, 1407 - 1414 (2009)25 October 2009 | doi:10.1038/nn.2414
Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways
Barbara Lorber1,2,4, Mariko L Howe1, Larry I Benowitz1,2,3 & Nina Irwin1,2
Mammalian sterile 20-like kinase-3b (Mst3b, encoded by Stk24), regulates axon outgrowth in embryonic cortical neurons in culture, but its role in vivo and in neural repair is unknown. Here we show that Mst3b mediates the axon-promoting effects of trophic factors in mature rat retinal ganglion cells (RGCs) and dorsal root ganglion (DRG) neurons, and is essential for axon regeneration in vivo. Reducing Mst3b levels using short hairpin RNA prevented RGCs and DRG neurons from regenerating axons in response to growth factors in culture, as did expression of a kinase-dead Mst3b mutant. Conversely, expression of constitutively active Mst3b enabled both types of neurons to extend axons without growth factors. In vivo, RGCs lacking Mst3b failed to regenerate injured axons when stimulated by intraocular inflammation. DRG neurons regenerating axons in vivo showed elevated Mst3b activity, and reducing Mst3b expression attenuated regeneration and p42/44 MAPK activation. Thus, Mst3b regulates axon regeneration in both CNS and PNS neurons.
1 Laboratories for Neuroscience Research in Neurosurgery and F.M. Kirby Neurobiology Center, Children's Hospital, Boston, Massachusetts, USA.
2 Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
3 Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
4 Present address: Centre for Brain Repair, University of Cambridge, Cambridge, UK.
