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JCI:逆转新生儿和成人脑损伤的新思路

2018-04-22 佚名 生物探索

4月16日,发表在《临床研究杂志》(JCI)上的文章为患有脑瘫、多发性硬化和痴呆等脑部疾病的儿童和成年人带来了福音。研究人员称,他们已经在大脑白质中发现了一种阻止器官在受伤后自我修复的能力的新分子,这一发现或离开发恢复正常脑功能的新疗法又近了一步。

“通过阻止这种分子的产生,我们可以创造一种有效的途径,让大脑继续其再生过程。这可能有助于限制与破坏性神经疾病相关的长期身心残疾。”论文主要作者之一Stephen Back博士说。

发现“坏演员”

透明质酸是人体内最大的分子之一,它填充细胞之间的空间,润滑关节,并积聚在脑白质的病变(或异常)中。众所周知,这种积聚会停止大脑的修复过程,从而对大脑的整体功能造成巨大的破坏。

为了更好地理解透明质酸造成的修复障碍,Back和他的同事们证实,虽然大脑损伤会将这些大分子分解成各种大小,但只有一个特定大小的片段会选择性地阻断促进修复所需的脑细胞的发育。

通过追踪阻止大脑修复的分子途径,研究人员发现这种特殊的片段还激活了一种叫做FoxO3的蛋白质,这种蛋白质阻断了开启修复过程的关键基因且这个路障(road block)还不允许其他强有力的维修信号绕过它。

Back 说:“我们已经确定了一个扮演‘坏演员’角色的分子。本质上,它劫持了免疫系统的分子机制,并重新利用它来关闭脑损伤后的大脑修复。虽然这种新分子可能不易在大脑中被检测到,但FoxO3可以作为一种可行的生物标记物,用于识别其在白质中的有害影响,从而为进一步的研究和靶向治疗创造机会,以完全逆转脑损伤对任何年龄段人群的影响。”

下一步

俄勒冈州国家灵长类动物研究中心神经科学部教授、研究合着者Larry Sherman博士说:“多年来,研究人员和临床医生都在努力理解和有效治疗与白质损伤相关的重大身体残疾,当前这一发现意味着,我们现在有可能开始寻找多种干预方法来促进大脑修复,而这些方法以前是无法使用的。”

未来,开发能够预防透明质酸片段产生的新药物是一个很有希望的方向。“此外,对大脑修复途径的新理解可能会为医疗保健专业人员提供新的见解,从而对干细胞移植等疗法产生积极影响。” Back补充道。

原始出处:

Taasin Srivastava, et al. A TLR/AKT/FoxO3 immune tolerance–like pathway disrupts the repair capacity of oligodendrocyte progenitors, J Clin Invest. doi.org/10.1172/JCI94158 , www.jci.org/articles/view/94158.

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    2019-03-16 晓辰
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    2019-03-06 智慧医人
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    2018-04-23 张新亮1853311252142e2fm

    好文献学习了

    0

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    2018-04-22 虈亣靌

    不错很喜欢很实用.值得推荐

    0

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