Title:MicroRNAs in CAG Trinucleotide Repeat Expansion Disorders: an Integrated Review of the Literature
Volume: 14
Issue: 2
Author(s): Laura Dumitrescu and Bogdan O. Popescu
Affiliation:
Keywords:
CAG, Huntington, microRNA, RNA interference, spinocerebellar, trinucleotide.
Abstract: MicroRNAs are small RNAs involved in gene silencing. They play important roles in
transcriptional regulation and are selectively and abundantly expressed in the central nervous
system. A considerable amount of the human genome is comprised of tandem repeating
nucleotide streams. Several diseases are caused by above-threshold expansion of certain
trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic,
CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations
of multiple coexisting pathways resulting in one common final consequence: selective
neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to
be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat
disorders is scarcely described, however microRNA dysregulation has been identified in these
diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis.
Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the
pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to
provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing
strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems
feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just
beginning.
