Azadiradione ameliorates polyglutamine expansion disease inDrosophilaby potentiating DNA binding activity of heat shock factor 1

• DOI: 10.18632/oncotarget.12930
• Publication Date: 2016-10-27T02:06:56Z
• Authors: Vinod K. Nelson; Asif Ali; Naibedya Dutta; Suvranil Ghosh; Manas Jana; Arnab Ganguli; Andrei Komarov; Soumyadip Paul; Vibha Dwivedi; Subhrangsu Chatte...; Nihar R. Jana; Subhash C. Lakhotia; Gopal Chakrabarti; Anup K. Misra; Subhash C. Mandal; Mahadeb Pal
• Keywords: Heat shock factor

Aggregation of proteins with the expansion polyglutamine tracts in brain underlies progressive genetic neurodegenerative diseases (NDs) like Huntington's disease and spinocerebellar ataxias (SCA). An insensitive cellular proteotoxic stress response to non-native protein oligomers is common such conditions. Indeed, upregulation heat shock factor 1 (HSF1) function its target chaperone expression has shown promising results animal models NDs. Using an HSF1 sensitive cell based reporter screening, we have isolated azadiradione (AZD) from methanolic extract seeds Azadirachta indica, a plant known for multifarious medicinal properties. We show that AZD ameliorates toxicity due aggregation fly great extent. All these effects are correlated activation genes. Notably, by independent HSP90 or proteasome function. Furthermore, directly interacts purified human high specificity, facilitates binding recognition sequence higher affinity. These unique findings qualify as ideal lead molecule consideration drug development against NDs affect millions worldwide.