Piperine modulates protein mediated toxicity in FXTAS through interacting expanded r(CGG)exp RNA

An expansion of CGG tandem repeats in 5' UTR of fragile X mental retardation 1 (FMR1) gene causes Fragile X-associated tremor/ataxia syndrome (FXTAS). The transcripts of these expanded repeats r(CGG)exp either form RNA foci or undergo the repeat-associated non-ATG (RAN) translation that produces toxic homopolymeric proteins in the neuronal cells. The discovery of the small molecule modulators that possess a strong binding affinity and high selectivity to these toxic expanded repeats RNA could be a promising therapeutic approach to cure the expanded repeat-associated neurological diseases. Therefore, here we sought to test the therapeutic potential of a natural alkaloid, Piperine by assessing its ability to bind and neutralize the toxicity of r(CGG)exp RNA motif. To accomplish this first, we have determined the affinity of Piperine with r(CGG)exp RNA using fluorescence-based binding assay and isothermal titration calorimetry assay. These assays showed that Piperine forms thermodynamically favourable intera...