The expanding biology of the C9orf72 nucleotide repeat expansion in neurodegenerative disease

被引：156

作者：

Haeusler, Aaron R. ^{[1
]}

Donnelly, Christopher J. ^{[2
,3
]}

Rothstein, Jeffrey D. ^{[4
,5
,6
]}

机构：

[1] Johns Hopkins Univ, Dept Biochem & Mol Biol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA

[2] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15260 USA

[3] Univ Pittsburgh, Live Lou Ctr ALS Res, Inst Brain, Pittsburgh, PA 15261 USA

[4] Johns Hopkins Univ, Sch Med, Brain Sci Inst, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

来源：

NATURE REVIEWS NEUROSCIENCE | 2016年 / 17卷 / 06期

基金：

美国国家卫生研究院;

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; T7; RNA-POLYMERASE; HEXANUCLEOTIDE REPEAT; G-QUADRUPLEX; GGGGCC REPEAT; R-LOOPS; ANTISENSE OLIGONUCLEOTIDE; MOTOR-NEURONS; NUCLEAR-RNA;

D O I：

10.1038/nrn.2016.38

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A nucleotide repeat expansion (NRE) within the chromosome 9 open reading frame 72 (C9orf72) gene was the first of this type of mutation to be linked to multiple neurological conditions, including amyotrophic lateral sclerosis and frontotemporal dementia. The pathogenic mechanisms through which the C9orf72 NRE contributes to these disorders include loss of C9orf72 function and gain-of-function mechanisms of C9orf72 driven by toxic RNA and protein species encoded by the NRE. These mechanisms have been linked to several cellular defects-including nucleocytoplasmic trafficking deficits and nuclear stress-that have been observed in both patients and animal models.

引用

页码：383 / U79

页数：13

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