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      The quest towards understanding the molecular pathogenesis of triplet repeat disorders: Huntingtons Disease and Fragile X-Associated Tremor and Ataxia Syndrome

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            Abstract

            Trinucleotide repeat disorders encompass a group of neurological diseases driven by unstable repeat expansions. Huntingtons disease (HD) is characterized by chorea and brain atrophy. The normal huntingtin protein contains 6-34 CAG repeats; however, upon a threshold effect of >36 repeats, the huntingtin protein acquires toxic mechanisms that are harmful to the cell. Fragile X-Associated Tremor and Ataxia (FXTAS) is characterized by tremor, ataxia and neuronal loss. The normal FMR1 gene contains 5-45 CGG repeats; however, upon a premutation CGG expansion of 55-200, FXTAS arises. A pathological hallmark of these disorders includes aggregate formation within the brain; suggestive of impaired protein and mRNA function. Furthermore, important molecules have been found to be sequestered into these aggregates withdrawing them from their normal roles. In this review, the ways mutant huntingtin and FMR1 mRNA aggregates induce intracellular dysfunction in HD and FXTAS is analyzed, specifically in the context of impaired neuronal processes and protein-protein interactions. Analysis revealed that huntingtin and FMR1 mRNA are involved in the regulation of multiple cellular pathways; and whose impaired function results in a detrimental domino-effect that is destructive to the cell. The understanding of these molecular processes hopes to identify potential targets towards the treatment of HD and FXTAS

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            Author and article information

            Journal
            ScienceOpen Preprints
            ScienceOpen
            24 July 2020
            Affiliations
            [1 ] University of Exeter
            Article
            10.14293/S2199-1006.1.SOR-.PPDKNVA.v1
            e4964190-f892-4f3c-8d3b-a5e73a1754db

            This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .


            Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
            Medicine
            genomic,medicine,cellular,biology,huntingtons,protein,huntington's disease,mutant protein,fragile x ,fragile x associated tremor and ataxia syndrome

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