Evidence for RNA-mediated toxicity in the fragile X-associated tremor/ataxia syndrome

被引:37
作者
Galloway, Jocelyn N. [1 ]
Nelson, David L. [2 ]
机构
[1] Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol & Human Genet, One Baylor Pl,Room 902EA, Houston, TX 77030 USA
关键词
FXTAS; intranuclear inclusion; neurodegeneration; premutation allele; riboCGG-mediated toxicity; RNA-binding protein;
D O I
10.2217/FNL.09.44
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Fragile X premutation carriers are at risk for developing a late-onset, progressive neurodegenerative disorder termed fragile X-associated tremor/ataxia syndrome (FXTAS). A growing body of evidence suggests the characteristic excess CGG repeat containing FMR1 mRNA observed in premutation carriers is pathogenic and leads to clinical features of FXTAS. The current model suggests premutation mRNA transcripts can induce the formation of intranuclear inclusions by the sequestration of RNA-binding proteins and other proteins. The sequestered proteins are prevented from performing their normal functions, which is thought to lead to the neuropathology-observed FXTAS. This paper discusses the existing evidence that microsatellite expansions at the level of RNA play a role in the disease pathogenesis of FXTAS and some of the approaches that may uncover downstream effects of expanded riboCGG expression.
引用
收藏
页码:785 / 798
页数:14
相关论文
共 106 条
[1]   Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS) [J].
Adams, J. S. ;
Adams, P. E. ;
Nguyen, D. ;
Brunberg, J. A. ;
Tassone, F. ;
Zhang, W. ;
Koldewyn, K. ;
Rivera, S. M. ;
Grigsby, J. ;
Zhang, L. ;
DeCarli, C. ;
Hagerman, P. J. ;
Hagerman, R. J. .
NEUROLOGY, 2007, 69 (09) :851-859
[2]  
Allingham-Hawkins SJ, 1999, AM J MED GENET, V83, P322, DOI 10.1002/(SICI)1096-8628(19990402)83:4<322::AID-AJMG17>3.0.CO
[3]  
2-B
[4]   Induction of inclusion formation and disruption of lamin A/C structure by premutation CGG-repeat RNA in human cultured neural cells [J].
Arocena, DG ;
Iwahashi, CK ;
Won, N ;
Beilina, A ;
Ludwig, AL ;
Tassone, F ;
Schwartz, PH ;
Hagerman, PJ .
HUMAN MOLECULAR GENETICS, 2005, 14 (23) :3661-3671
[5]   Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: Newly described fronto-subcortical dementia [J].
Bacalman, S ;
Farzin, F ;
Bourgeois, JA ;
Cogswell, J ;
Goodlin-Jones, BL ;
Gane, LW ;
Grigsby, J ;
Leehey, MA ;
Tassone, F ;
Hagerman, RJ .
JOURNAL OF CLINICAL PSYCHIATRY, 2006, 67 (01) :87-94
[6]   The DNA repair-ubiquitin-associated HR23 proteins are constituents of neuronal inclusions in specific neurodegenerative disorders without hampering DNA repair [J].
Bergink, Steven ;
Severijnen, Lies-Anne ;
Wijgers, Nils ;
Sugasawa, Kaoru ;
Yousaf, Humaira ;
Kros, Johan M. ;
van Swieten, John ;
Oostra, Ben A. ;
Hoeijmakers, Jan H. ;
Vermeulen, Wim ;
Willemsen, Rob .
NEUROBIOLOGY OF DISEASE, 2006, 23 (03) :708-716
[7]   Fragile X-associated tremor/ataxia syndrome in sisters related to X-inactivation [J].
Berry-Kravis, E ;
Potanos, K ;
Weinberg, D ;
Zhou, LL ;
Goetz, CG .
ANNALS OF NEUROLOGY, 2005, 57 (01) :144-147
[8]   Instability of a (CGG)98 repeat in the Fmr1 promoter [J].
Bontekoe, CJM ;
Bakker, CE ;
Nieuwenhuizen, IM ;
van der Linde, H ;
Lans, H ;
de Lange, D ;
Hirst, MC ;
Oostra, BA .
HUMAN MOLECULAR GENETICS, 2001, 10 (16) :1693-1699
[9]   CGG-repeat length and neuropathological and molecular correlates in a mouse model for fragile X-associated tremor/ataxia syndrome [J].
Brouwer, Judith R. ;
Huizer, Karin ;
Severijnen, Lies-Anne ;
Hukema, Renate K. ;
Berman, Robert F. ;
Oostra, Ben A. ;
Willemsen, Rob .
JOURNAL OF NEUROCHEMISTRY, 2008, 107 (06) :1671-1682
[10]  
Brunberg JA, 2002, AM J NEURORADIOL, V23, P1757