APPLICATION OF BIOMOLECULES IN HUNTINGTON'S DISEASE: AN IN SILICO ANALYSIS OF HUNTINGTIN (HTT) GENE WITH DRUGS

Abstract

Huntington’s disease (HD) is an inherited progressive and severe neurodegenerative disorder that commonly starts in mid age, predominantly in striatum and is described by involuntary movements, personality changes and dementia. The mutated gene responsible for expression of polyglutamine repeats in huntingtin proteins, Contains a trinucleotide CAG repeat expansion within its coding region. The molecular mechanisms involved in cell death due to the toxic effect of mutant huntingtin is unknown, but a strong body of evidence shows that mutant protein in HD misfolds and accumulate into aggregate and the huntingtin protein is fragmented in affected individuals, htt exon1, a fragment of huntingtin which forms amyloid fibril aggregates, that might be cause of toxicity. Tetrabenazine (TBZ) is the only US Food and Drug approved drug for HD patient. The objective of this study is to identify newer antipsychotic biomolecules with adequate efficacy and more favorable adverse effect than tetrabenazine. Some natural products like Curcumin, Berberine, Aripiprazole, Clozapine, Olanzapine, Pridopidine, Quetiapine, Rilmenidine and Tiapride are shown to be effective in relieving the adverse effect of accumulated misfolded proteins in several neurodegenerative diseases. Hence, these natural products can be promising therapeutic approach to Huntington’s disease (HD). Here, in silco molecular docking was performed against huntingtin gene (htt) using antipsychotic biomolecules and furthermore docking results was compared with docking result of tetrabenazine.