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J Neurosci:癌症治疗药物RGFP966可有助于寻回记忆(附评论)

2015-10-06 MedSci MedSci原创

1

梅斯医学(MedSci)小编题记——

临床药物的跨界应用将越来越普遍!阿司匹林这种解热镇痛药物彻底跨界的虽然不多,但是跨界应用并不少见。只要是背后的机制相同,就有可能被跨界,甚至成为更好的药物。例如,导致当年豹肢儿的沙利度胺,现在在多发骨髓瘤,肝癌,甚至肠道克隆病的治疗中,有望大展拳脚(JAMA:沙利度胺可提高儿童和青少年难治性克罗恩病缓解率)!免疫抑制剂依维莫司,现在大量研究用多种肿瘤的治疗,尤其是神经内分泌肿瘤(ECC 2015:依维莫司能显著延长无功能的胃肠道和肺神经内分泌肿瘤(RADIANT-4研究)),以及对一些慢性退行性病变的研究也在进行,其背后的机制是激活细胞自噬作用。大名鼎鼎的青蒿素衍生物,现在正在研究对肿瘤的治疗作用(PLoS One:双氢青蒿素诱导肝癌细胞凋亡);还有一些抗精神病药物,惊奇的发现,可能对肿瘤干细胞具有抑制作用(Cell:硫利达嗪成功消灭人体白血病干细胞),同样,在肿瘤干细胞上发现与情绪有关的多巴胺受体(Cell:肿瘤干细胞的新生物标志物多巴胺受体);二甲双胍用于减肥,抗癌和辅助生殖;贝伐单抗主要用于肿瘤抗血管新生,但实际上对黄斑病变同样具有很好的效果,因为背后都是VEGF在起作用。降糖药物吡格列酮可能有助于白血病的治疗,因此,背后PPARγ是相同的。治疗类风湿性关节炎的托法替尼,近来发现对白癜风有很好的潜在效果(JAMA Dermatol:托法替尼(Tofacitinib)——白癜风治疗的新希望 );乌司他丁作为急诊用药,现在可能发现对癌症有治疗作用哦。当然,还有一些药是因为“不良反应”而开设新的用途潜能,如红霉素的胃肠道严重不良反应,现在用它作为胃动力药物。

亲们,当您阅读到这篇文献时,也做一些联想吧,也许会有意想不到的效果哦,大家多读读MedSci上资讯,或关注微信,或下载APP,一点联想,乐趣无穷。

正文:

老年痴呆症和阿尔茨海默症可导致机体的记忆力丧失,不仅会影响机体处理新的记忆的能力,还会影响机体的运动功能。近日,发表于《神经科学杂志》的一项新的研究表明,癌症治疗中使用的药物或可有助于恢复机体处理新记忆的能力。

RGFP966,组蛋白去乙酰化酶(HDAC)抑制剂,目前用于癌症的治疗,可防止基因突变以抑制正常细胞转变为癌细胞。

大脑中的RGFP966可使神经元的塑性 更高,更好的处理连接并创建积极 改变以提高记忆。

由于将信息从一个神经元传递到另一个神经元的突触变得不再强壮和稳定,因此如老年痴呆症及阿尔茨海默症等疾病可导致脑细胞的萎缩和死亡。

该研究第一作者Kasia M. Bieszczad博士表示,一旦一个人处于疾病(阿尔茨海默症及其他神经性的疾病)的进展时期,则患者的记忆创造力很差或完全没有。目前为止,尚未有可逆转此情况的治疗方法。

但是,Bieszczad的研究团队发现,对小鼠应用RGFP966后可使小鼠更适应它们所听到的,保留更多的记忆,并可建立新的联系可允许这些记忆在神经元之间传递。

采用奖励的方法训练小鼠听声音,与未接受药物治疗的小鼠相比,接受药物治疗的训练后的小鼠可听到和正确回应这些声音的频率更高。

接受药物治疗的大鼠在训练过程中也可更好的调整相关的声音信号,表明药物可有助于机体更有效的建立大脑处理和存储有意义的声音,这对人类的说话和语言同样至关重要。

研究人员表示,提高处理声音的能力可使得小鼠大脑中的神经元更好的重组和创造新的途径,因而使得学习到的更多的信息转变为长期的记忆。

研究人员希望此药物可帮助“重塑大脑”,保持神经元的活性并可创造详细且具体的记忆,即使是在最严重的病例中。

该研究小组建议,该药物不应仅限于阿尔茨海默症及老年痴呆症的治疗,还应用于如受伤后或人工耳蜗植入后帮助患者再次说话。该药还可帮助那些语言学习能力迟缓的人甚至是尝试学习第二中语言的人。

Bieszczad说道:“人们通常会对细节记忆有限;而不是我们所看到的,所听到的,所感觉到的。本研究所发现的是记忆可变为更接近实际经历的投照,而不是稀疏的、有限的、不准确的。”

原始出处:

Bieszczad KM, Bechay K, Rusche JR, Jacques V, Kudugunti S, Miao W, Weinberger NM, McGaugh JL, Wood MA.Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation. J Neurosci. 2015 Sep 23;35(38):13124-32. 

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    2015-10-11 chinayinhan

    学习了,很好

    0

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    2015-10-11 chinayinhan

    学习了,很好

    0

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    2015-10-11 chinayinhan

    学习了,很好

    0

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    2015-10-11 chinayinhan

    学习了,很好

    0

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    2015-10-11 chinayinhan

    学习了,很好

    0

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    2015-10-11 chinayinhan

    学习了,很好

    0

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    2015-10-11 chinayinhan

    学习了,很好

    0

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