FXTAS: a bad RNA and a hope for a cure

Abstract

Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a newly identified neurodegenerative disorder due to intermediate expansion of trinucleotide CGG repeats (55 – 200 repeats) in the 5′ untranslated region (UTR) of the Fragile X mental retardation 1 (FMR1) gene. FXTAS is now considered to be one of the most common inherited neurodegenerative disorders in males. Objective: To examine the future of potential therapies for this late-onset disease. Methods: Examination of relevent literature. Results/conclusions: Accumulating evidence indicates that overproduced riboCGG repeats in the 5′ UTR of FMR1 mRNA are toxic. Recently, proteins that bind specifically to rCGG repeats were identified. Progress in understanding the molecular pathogenesis of FXTAS, plus the availability of different animal models are discussed.

Keywords::

• animal models
• CUGBP1
• FXTAS
• hnRNP A2/B1
• non-coding RNA
• Pur α
• rCGG repeats
• RNA toxicity
• trinucleotide repeats

Acknowledgement

P Jin is supported by NIH grants R01 NS051630 and R01 MH076090 and is the recipient of a Beckman Young Investigator Award and a Basil O'Connor Scholar Research Award and is an Alfred P Sloan Research Fellow in Neuroscience.

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