Small Molecules Targeting Repeat Sequences Causing Neurological Disorders

Abstract

Expansion of specific repeat sequences in human genomic DNA causes neurological disorders if the expanded repeats exceed a certain threshold. Mechanism of the repeat expansions and the disease pathogenesis involves the formation of noncanonical structures by the repeat DNAs and their transcripts. Small molecules targeting fluctuated regions of these repeat structures have potential as tools for studying disorders induced by aberrant expansion of repeat sequences and eventually for the development of molecules toward therapeutics. Several groups have focused on developing small molecules targeting the structurally fluctuated regions of DNA and RNA repeat structures and succeeded in discovering several small molecules that bind to the repeat sequences of neurological disorders. In this chapter, small molecules binding to CAG repeats causing Huntington’s disease (HD), CUG repeats causing myotonic dystrophy type 1 (DM1), and UGGAA repeats causing spinocerebellar ataxia type 31 (SCA31) were discussed. Moreover, their remarkable effects on the disease in cellular and animal model systems demonstrated the potential of small molecules as drugs for treating neurological diseases caused by repeat sequences.