Deciphering the enigma of human poly(Q) disorders: Contribution of Drosophila melanogaster

Abstract

 Poly(Q) disorders includes neurodegenerative disorders associated with irreversible  loss of specific neurons in adult brain. The causative factor has been identified as the abnormal expansion of CAG repeats in protein coding region of the gene which leads to formation of protein Inclusion Bodies (IBs) and altered cellular physiology. The molecular pathogenesis of poly(Q) disease involves protein mis-folding, aggregate formation, blockage of axonal transport, mitochondrial dysfunction and global transcriptional dysregulation. Formation of inclusion bodies is a hallmark and common characteristic feature of all poly(Q) disorders. In view of limitation attached with human genetics, Drosophila has emerged as an excellent system to model the human neurodegenerative disorders due to availability of flexible yet powerful genetic tools and owing to the similarity between some of the fundamental cellular processes with humans. Drosophila system has been extensively utilized not only to decipher the mechanistic detail of diseases pathogenesis but also to screen several genetic and chemical modifiers which could potentially help in designing novel therapeutic strategies. The Drosophila melanogaster, thus, expected to contribute meaningfully towards novel discoveries to design novel therapeutic strategies to combat the devastating human neurodegenerative disorders.