...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Physiology versus pathology in Parkinson's disease
【24h】

Physiology versus pathology in Parkinson's disease

机译：帕金森氏病的生理学与病理学

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Over the last few years, human genetics has provided a series of invaluable entry points to understanding the pathogenesis rnof Parkinson's disease (PD). Relative to dominantly inherited forms of PD caused by mutations in the proteins α-synuclein and leucine-rich repeat kinase rn2 (LRRK2), recessive forms of PD do not seem to bear as close a resemblance to the sporadic disorder. Mutations in parkin produce a distinctive, early onset clinical syndrome with slower progression than the idiopathic disorder. Parkin functions as an E3 ubiquitin ligase, suggesting a role in targeting to the proteasome and protein turnover. Considering this biochemical activity, it is surprising that the pathology associated with mutations in parkin shows no Lewy bodies or obvious protein deposits. Indeed, ubiquitination by parkin may control other cellular processes such as endocytosis. Nonetheless, mutations in parkin do result in the loss of midbrain dopamine neurons. Mutations in the protein DJ-1 implicated in the response to oxidative stress also produce recessive parkinsonism, but there is very little if any pathology available. Although the condition responds to dopamine replacement therapy, we do not know whether it actually involves a loss of dopamine neurons. Similarly, mutations in the PTEN-induced putative kinase 1 (PINK1), the subject of the paper by Kitada et al. in a recent issue of PNAS, cause a form of recessive parkinsonism, but its pathological basis also remains to be characterized. Nonetheless, a significant number of patients with later-onset parkinsonism that strongly resembles idiopathic PD have heterozygous, or occasionally homozygous, rnmutations in parkin, DJ-1, and PINK1, supporting their relationship to the sporadic disorder.
机译：在过去的几年中，人类遗传学提供了一系列宝贵的切入点，以了解帕金森氏病（PD）的发病机理。相对于由蛋白质α-突触核蛋白和富含亮氨酸的重复激酶rn2（LRRK2）突变引起的PD的显性遗传形式，PD的隐性形式似乎与散发性疾病没有相似之处。相比于特发性疾病，Parkin突变会产生一种独特的，较早发作的临床综合征，其进展较慢。帕金蛋白起着E3泛素连接酶的作用，暗示着在靶向蛋白酶体和蛋白质更新中的作用。考虑到这种生化活性，令人惊讶的是，与帕金蛋白突变相关的病理显示没有路易体或明显的蛋白质沉积。确实，帕金蛋白的泛素化可以控制其他细胞过程，例如胞吞作用。尽管如此，帕金菌的突变确实会导致中脑多巴胺神经元的丢失。与氧化应激反应有关的蛋白质DJ-1突变也会产生隐性帕金森病，但几乎没有病理学可用。尽管该病情对多巴胺替代疗法有反应，但我们不知道它是否确实涉及多巴胺神经元的丧失。类似地，Kitada等人的论文主题是PTEN诱导的假定激酶1（PINK1）中的突变。在最近一期的PNAS中，会引起某种形式的隐性帕金森病，但其病理学基础也有待确定。尽管如此，仍有大量与特发性PD非常相似的后发性帕金森氏病患者在Parkin，DJ-1和PINK1中出现杂合或偶发纯合突变，支持他们与散发性疾病的关系。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号