eLife:对帕金森病理论提出质疑

2018-07-10 小通 生物通

早在200多年前,一位英国医生首次描述了帕金森氏症,这种神经退行性疾病的确切病因尚不明确。最近,《eLife》一项由巴塞尔大学Henning Stahlberg领导的研究指出,之前我们对这种疾病的理解可能是错误的。


早在200多年前,一位英国医生首次描述了帕金森氏症,这种神经退行性疾病的确切病因尚不明确。最近,《eLife》一项由巴塞尔大学Henning Stahlberg领导的研究指出,之前我们对这种疾病的理解可能是错误的。

手脚不停颤抖、肌肉虚弱、动作缓慢……这些都是帕金森症状。全世界有超过600万人患有帕金森。研究人员发现,患者脑内多巴胺生产神经元逐渐消亡,由此产生的神经递质缺陷导致运动机能和认知能力障碍。

疑点:蛋白质纤维导致帕金森?

目前,普遍认为α-突触核蛋白是帕金森的触发因素之一。这种蛋白一旦聚集、形成针状原纤维(fibrils)并在神经细胞中积累沉淀为路易氏小体(Lewy bodies),就会对脑细胞造成毒性。巴塞尔大学的Henning Stahlberg教授带领的一队科学家与Hoffmann-La Roche有限公司和苏黎世联邦理工大学的科研人员合作,在试管中人工合成α-突触核蛋白原纤维,在原子水平首次可视化了这种物质的三维结构。

在一些先天性帕金森中,患者携带α-突触核蛋白遗传缺陷。据推测,突变导致了蛋白质错误折叠,从而形成有毒原纤维。“然而,我们的3D观察结果表明,突变的α-突触核蛋白无法形成有毒的原纤维,”Stahlberg说。“相反,大多数突变会阻碍原纤维结构形成。简而言之,如果是原纤维结构导致了帕金森,那么遗传缺陷似乎是用来预防疾病的。这很矛盾。因此,很有可能是别的类型的原纤维或其他形式的蛋白质触发了患者疾病。”

提出新问题

α-突触核蛋白遗传缺陷究竟影响的是什么?它会导致不同形式的蛋白质聚集吗?原纤维对神经细胞的作用是什么?为什么积累原纤维的细胞会死亡?至今为止,α-突触核蛋白的确切生理功能尚未完全阐明,为开发缓解神经退行性疾病症状的药物,这些概念迫切需要解决。

原始出处:

Ricardo Guerrero-Ferreira et al.Cryo-EM structure of alpha-synuclein fibrils.RESEARCH ARTICLE Jul 3, 2018

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    2019-06-04 膀胱癌
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    2019-03-08 clmlylxy
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    2018-11-10 saikp
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    2018-07-11 131****1460

    学习了受益匪浅

    0

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    2018-07-10 清风拂面

    谢谢分享学习

    0

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渐冻症、老年痴呆、肌肉萎缩、小脑萎缩……这些原本与帕金森病不同的疾病,却被公众画上等号。在世界帕金森病日(4月11日)前夕,记者将“你了解帕金森病吗”这一问题随机抛给同事、朋友、邻居等人,得到了上述答案。

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据新华社马德里 5 月 27 日电 西班牙研究人员日前报告说,他们首次在视网膜上检测到了与帕金森病发病密切相关的阿尔法—突触核蛋白,这一发现有望应用于帕金森病等神经退行性疾病的早期诊断。

西北帕金森病防治联盟在西安成立

5月12日,“西北帕金森病防治联盟”在西安正式成立,将帮助西北地区各级医院建立规范的帕金森专病门诊,组织开展帕金森病疑难病例会诊,极大地促进西北地区帕金森病诊疗水平的全面提高。当日下午,来自西北地区各省市从事帕金森病诊疗工作的专家、教授50余人参加了西北帕金森病防治联盟揭牌仪式。“由于特殊的地理位置,西北地区帕金森病诊治水平参差不齐,许多偏远地区的帕金森病患者没有得到规范的诊治。”采访中,西安交通