Cellular DNAJBs are selectively associated with proteotoxic stress and underlying mechanisms in neurodegenerative conditions

Molecular chaperones are an integral part of protein quality control systems and are induced by various environmental, chemical, heat and genetic stress factors. In neurodegenerative diseases, where protein misfolding and aggregation are the hallmark features, several stress factors are involved in the initiation of disease pathogenesis; however, the response of molecular chaperones under these conditions is not well understood. In the present study, the expression profile of major chaperone HSPA and its co-chaperone DNAJ proteins are analysed under oxidative, proteotoxic and heat stress conditions to provide a comparative profile of their expression. Different stress inducers resulted in dynamic and selective expression of HSPA and DNAJ proteins. A unique molecular imprint of HSPA1 (HSP70), HSPA8 (HSC70) and HSPH1(HSP110) was observed for proteotoxic conditions. Similarly, the DNAJB1 protein was upregulated in all stress conditions, while the specificity of DNAJB8 was observed for proteotoxic stress. The dynamic expression of chaperones was regulated by HSF1 and NRF2 transcriptional regulators. HSF1 expression was increased in all conditions, while NRF2 activation was selective for oxidative and heat stress. The results suggested molecular imprints of chaperones for specific stress conditions may assist in selecting the appropriate targets for modifications in protein aggregation-associated diseases.