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

被引：157

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

共 148 条

[41] Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers [J].

Gendron, Tania F. ;

van Blitterswijk, Marka ;

Bieniek, Kevin F. ;

Daughrity, Lillian M. ;

Jiang, Jie ;

Rush, Beth K. ;

Pedraza, Otto ;

Lucas, John A. ;

Murray, Melissa E. ;

Desaro, Pamela ;

Robertson, Amelia ;

Overstreet, Karen ;

Thomas, Colleen S. ;

Crook, Julia E. ;

Castanedes-Casey, Monica ;

Rousseau, Linda ;

Josephs, Keith A. ;

Parisi, Joseph E. ;

Knopman, David S. ;

Petersen, Ronald C. ;

Boeve, Bradley F. ;

Graff-Radford, Neill R. ;

Rademakers, Rosa ;

Lagier-Tourenne, Clotilde ;

Edbauer, Dieter ;

Cleveland, Don W. ;

Dickson, Dennis W. ;

Petrucelli, Leonard ;

Boylan, Kevin B. .

ACTA NEUROPATHOLOGICA, 2015, 130 (04) :559-573

[42] Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS [J].

Gendron, Tania F. ;

Bieniek, Kevin F. ;

Zhang, Yong-Jie ;

Jansen-West, Karen ;

Ash, Peter E. A. ;

Caulfield, Thomas ;

Daughrity, Lillian ;

Dunmore, Judith H. ;

Castanedes-Casey, Monica ;

Chew, Jeannie ;

Cosio, Danielle M. ;

van Blitterswijk, Marka ;

Lee, Wing C. ;

Rademakers, Rosa ;

Boylan, Kevin B. ;

Dickson, Dennis W. ;

Petrucelli, Leonard .

ACTA NEUROPATHOLOGICA, 2013, 126 (06) :829-844

[43]

Gijselinck I., 2015, MOL PSYCHIAT

[44] A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study [J].

Gijselinck, Ilse ;

Van Langenhove, Tim ;

van der Zee, Julie ;

Sleegers, Kristel ;

Philtjens, Stephanie ;

Kleinberger, Gernot ;

Janssens, Jonathan ;

Bettens, Karolien ;

Van Cauwenberghe, Caroline ;

Pereson, Sandra ;

Engelborghs, Sebastiaan ;

Sieben, Anne ;

De Jonghe, Peter ;

Vandenberghe, Rik ;

Santens, Patrick ;

De Bleecker, Jan ;

Maes, Githa ;

Baumer, Veerle ;

Dillen, Lubina ;

Joris, Geert ;

Cuijt, Ivy ;

Corsmit, Ellen ;

Elinck, Ellen ;

Van Dongen, Jasper ;

Vermeulen, Steven ;

Van den Broeck, Marleen ;

Vaerenberg, Carolien ;

Mattheijssens, Maria ;

Peeters, Karin ;

Robberecht, Wim ;

Cras, Patrick ;

Martin, Jean-Jacques ;

De Deyn, Peter P. ;

Cruts, Marc ;

Van Broeckhoven, Christine .

LANCET NEUROLOGY, 2012, 11 (01) :54-65

[45] Depletion of Cognate Charged Transfer RNA Causes Translational Frameshifting within the Expanded CAG Stretch in Huntingtin [J].

Girstmair, Hannah ;

Saffert, Paul ;

Rode, Sascha ;

Czech, Andreas ;

Holland, Gudrun ;

Bannert, Norbert ;

Ignatova, Zoya .

CELL REPORTS, 2013, 3 (01) :148-159

[46] Dipeptide repeat protein inclusions are rare in the spinal cord and almost absent from motor neurons in C9ORF72 mutant amyotrophic lateral sclerosis and are unlikely to cause their degeneration [J].

Gomez-Deza, Jorge ;

Lee, Youn-Bok ;

Troakes, Claire ;

Nolan, Matthew ;

Al-Sarraj, Safa ;

Gallo, Jean-Marc ;

Shaw, Christopher E. .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2015, 3 :38

[47] The GAA•TTC triplet repeat expanded in Friedreich's ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner [J].

Grabczyk, E ;

Usdin, K .

NUCLEIC ACIDS RESEARCH, 2000, 28 (14) :2815-2822

[48] C9orf72 nucleotide repeat structures initiate molecular cascades of disease [J].

Haeusler, Aaron R. ;

Donnelly, Christopher J. ;

Periz, Goran ;

Simko, Eric A. J. ;

Shaw, Patrick G. ;

Kim, Min-Sik ;

Maragakis, Nicholas J. ;

Troncoso, Juan C. ;

Pandey, Akhilesh ;

Sattler, Rita ;

Rothstein, Jeffrey D. ;

Wang, Jiou .

NATURE, 2014, 507 (7491) :195-+

[49] Nuclear export inhibitors avert progression in preclinical models of inflammatory demyelination [J].

Haines, Jeffery D. ;

Herbin, Olivier ;

de la Hera, Belen ;

Vidaurre, Oscar G. ;

Moy, Gregory A. ;

Sun, Qingxiang ;

Fung, Ho Yee Joyce ;

Albrecht, Stefanie ;

Alexandropoulos, Konstantina ;

McCauley, Dilara ;

Chook, Yuh Min ;

Kuhlmann, Tanja ;

Kidd, Grahame J. ;

Shacham, Sharon ;

Casaccia, Patrizia .

NATURE NEUROSCIENCE, 2015, 18 (04) :511-+

[50] Lack of C9ORF72 coding mutations supports a gain of function for repeat expansions in amyotrophic lateral sclerosis [J].

Harms, Matthew B. ;

Cady, Janet ;

Zaidman, Craig ;

Cooper, Paul ;

Bali, Taha ;

Allred, Peggy ;

Cruchaga, Carlos ;

Baughn, Michael ;

Libby, Ryan T. ;

Pestronk, Alan ;

Goate, Alison ;

Ravits, John ;

Baloh, Robert H. .

NEUROBIOLOGY OF AGING, 2013, 34 (09) :2234.e13-2234.e19

← 1 2 3 4 5 6 7 8 9 10 →