Milestones in ataxia.
Milestones in ataxia.
复制标题
DOI：
10.1002/mds.23559
复制
发表时间：
2011-05
影响因子：
8.6
通讯作者：
Paulson, Henry
中科院分区：
文献类型：
--
作者：
Klockgether, Thomas;Paulson, Henry
关键词：
在过去的25年里，在破译共济失调的遗传和分子基础方面取得了巨大的进展，从而提高了对其发病机制的理解。这一时期最重要的里程碑是克隆了与常见的脊髓小脑共济失调（SCA）、共济失调毛细血管扩张症（AT）和弗里德赖希共济失调（FRDA）相关的基因。迄今为止，已确定了30多个SCA和20个隐性共济失调的致病突变。此外，有许多获得性共济失调与明确的分子原因，使整个数目的不同共济失调疾病超过50和可能接近100。尽管存在这种巨大的异质性，但仍有一些反复出现的病理生理学主题突出。这些包括蛋白质聚集、蛋白质稳态失败、离子通道功能扰动、DNA修复缺陷和线粒体功能障碍。最常见的共济失调疾病的临床表型已经确定，并且正在进行的大型观察性试验中研究其自然史。共济失调的有效治疗仍然缺乏。然而，新的药物靶点正在研究中，预计共济失调的治疗试验将越来越多。
The past 25 years have seen enormous progress in the deciphering of the genetic and molecular basis of ataxias resulting in an improved understanding of their pathogenesis. The most significant milestones during this period were the cloning of the genes associated with the common spinocerebellar ataxias (SCAs), ataxia telangiectasia (AT) and Friedreich ataxia (FRDA). To date, the causative mutations of more than 30 SCAs and 20 recessive ataxias have been identified. In addition, there are numerous acquired ataxias with defined molecular causes so that the entire number of distinct ataxia disorders exceeds 50 and possibly approaches 100. Despite this enormous heterogeneity, a few recurrent pathopyhsiological themes stand out. These include protein aggregation, failure of protein homoestasis, perturbations in ion channel function, defects in DNA repair and mitochondrial dysfunction. The clinical phenotypes of the most common ataxia disorders have been firmly established, and their natural history is being studied in ongoing large observational trials. Effective therapies for ataxias are still lacking. However, novel drug targets are under investigation, and it is expected that there will be an increasing number of therapeutic trials in ataxia.
登录
查看更多内容
影响因子：
4.4
作者：
PAPP, MI;KAHN, JE;LANTOS, PL
通讯作者：
LANTOS, PL
影响因子：
158.5
作者：
Durr, A;Cossee, M;Koenig, M
通讯作者：
Koenig, M
影响因子：
14.5
作者：
Anheim, M.;Monga, B.;Koenig, M.
通讯作者：
Koenig, M.
DOI：
10.1523/jneurosci.3909-08.2008
发表时间：
2008-11-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen X;Tang TS;Tu H;Nelson O;Pook M;Hammer R;Nukina N;Bezprozvanny I
通讯作者：
Bezprozvanny I
影响因子：
--
作者：
Lynch, David R.;Perlman, Susan L.;Meier, Thomas
通讯作者：
Meier, Thomas