Background: Several dominant neurodegenerative disorders result from alleles carrying expanded stretch of polyglutamine (polyQ) tracts in the encoded proteins, which become toxic and form insoluble cytoplasmic and/or nuclear aggregates or “inclusion bodies” in the affected neuronal cells. Purpose: Present study identified Hsp60D, a member of the Drosophila Hsp60 family, as a novel modifier of neurodegeneration in fly models of polyQ disorders, viz., Spinocerebellar Ataxia type 3 (SCA3, caused by mutated MJDtr-Q78 allele) or the 127Q model. Methods: Immunostaining of third instar larval eye discs was carried out and the eye discs of 50-hours old pupae of different genotypes were stained with Phalloidin-Rhodamine to examine the organization of actin filaments in ommatidial units. The nail polish imprints of adult eye surfaces were examined and the assay was performed using a glass Y-maze. Results: We showed that the reduction in the cellular levels of Hsp60D protein through directed RNAi in the polyQ expressing developing eye cells not only improved external eye morphology, retinal structure and vision, but also reduced the number of inclusion bodies and the associated expression of Hsp70. Conclusion: Our results suggest that Hsp60D may be required for folding of polypeptides with polyQ stretches so that in its absence, due to targeted RNAi, the expanded polyQ polypeptides fail to fold in a manner that can produce the toxic inclusion bodies.

doi : 10.5214/ans.0972.7531.2010.170104

Competing interests: None.  Source of Funding: DBT, DST, CSIR

Received Date: 29 Sept 2009     Revised Date: 05 Nov 2009     Accepted Date: 23 Nov 2009