RNA toxicity in tandem nucleotide repeats mediated neurodegenerative disorders

Abstract Over 40 neurological and neuromuscular disorders like Huntington's disease, muscular dystrophy, amyotrophic lateral sclerosis and a range of ataxias arise due to short nucleotide repeats(STRs) expansion where neurodegeneration is a common phenomenon. These short nucleotide repeats are hypervariable regions and can expand up to thousands of times in exonic or non-coding regions of diverse genes. The expansion beyond a particular length of nucleotide repeats is pathogenic which varies in different tandem nucleotide repeat (TNR) associated disorders. These STR expansions may lead to the loss of host gene function, toxic polypeptide production (canonical or non-canonical translation or both) and/or nuclear RNA foci formation. Of these, here we are bringing attention towards the very common and extensively explored pathological mechanism in these diseases, i.e., RNA mediated toxicity. Targeting the repeat containing RNA using various methods like aniti-sense oligonucleotides, small molecule inhibitors of abnormal RNA structures, etc. has been determined as one of the promising therapeutic tools for reversing the disease phenotype on the cellular and other model systems.