Huntington's disease (HD) is a neurodegenerative disorder that is caused by 
abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA 
contains expanded CAG repeats that translate into a mutant huntingtin protein. 
This expanded CAG repeat also causes mis-splicing of pre-mRNA due to 
sequestration of muscle blind like-1 splicing factor (MBNL1), and thus both of 
these elicit the pathogenesis of HD. Targeting the onset as well as progression 
of HD by small molecules could be a potent therapeutic approach. We have 
screened a set of small molecules to target this transcript and found Myricetin, 
a flavonoid, as a lead molecule that interacts with the CAG motif and thus 
prevents the translation of mutant huntingtin protein as well as sequestration 
of MBNL1. Here, we report the first solution structure of the complex formed 
between Myricetin and RNA containing the 5'CAG/3'GAC motif. Myricetin interacts 
with this RNA via base stacking at the AA mismatch. Moreover, Myricetin was also 
found reducing the proteo-toxicity generated due to the aggregation of 
polyglutamine, and further, its supplementation also improves neurobehavioral 
deficits in the HD mouse model. Our study provides the structural and 
mechanistic basis of Myricetin as an effective therapeutic candidate for HD and 
other polyQ related disorders.