Reduced expression of dMyc mitigates Tau^V337M mediated neurotoxicity by preventing the Tau hyperphosphorylation and inducing autophagy in Drosophila.

Tauopathies such as Alzheimer's disease (AD), Pick's disease (PiD), Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) etc. represent a group of age-related neurodegenerative disorders in which tau protein loses its normal conformation mostly due to hyperphosphorylation and subsequent formation of the aggregates of defined shapes, known as Neurofibrillary Tangles (NFTs). We have demonstrated earlier that reduced dosage of dmyc (Drosophila homolog of human cmyc proto-oncogene) restricts tau^WT mediated disease pathogenesis by regulating the phosphorylation status of tau. We demonstrate further that the downregulation of dmyc also alleviates the mutant human-tau (tau^V337M) mediated neurotoxicity in Drosophila by improving disease defects. Moreover, tissue-specific downregulation of dmyc also induces cellular autophagy which facilitates the disposal of misfolded proteins via lysosome-mediated proteostasis. Our findings demonstrate the capability of dmyc in the suppression of different forms of human tauopathies in Drosophila disease models. Interestingly, due to the conserved characteristics of dmyc/cmyc across the animal kingdom, our study strengthens the possibility of utilizing this gene as an effective drug target against tauopathies. Copyright © 2019 Elsevier B.V. All rights reserved.

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