Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P10636 (
tau protein
)
5,110
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Formation of Neurofibrillary Tangles (NFTs) in neuronal tissues has been implicated as the hallmark of disease pathogenesis and tau mediated toxicity in human and mammalian models. However, previous studies had failed to correlate NFT formation with pathogenesis of human neuronal tauopathies in Drosophila disease models. Though, a recent report suggests formation of tau mediated NFTs like structures confined to dopaminergic neurons in Drosophila adult brain; by utilizing various approaches, we demonstrate distinct and recurrent formation of NFTs in Drosophila neuronal tissues upon expression of wild type or mutant isoforms of human
tau protein
, and this appears as the key mediator of the pathogenesis of human neuronal tauopathy in Drosophila. Further, we show that tissue specific downregulation of dMyc (Drosophila homolog of human c-myc
proto-oncogene)
alleviates h-tau mediated cellular and functional deficits by restricting the formation of NFTs in neuronal tissues. Therefore, our findings provide very critical and novel insights about pathogenesis of human neuronal tauopathies in Drosophila disease models.
...
PMID:Targeted downregulation of dMyc restricts neurofibrillary tangles mediated pathogenesis of human neuronal tauopathies in Drosophila. 2852 46
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.
...
PMID:Reduced expression of dMyc mitigates Tau
V337M
mediated neurotoxicity by preventing the Tau hyperphosphorylation and inducing autophagy in Drosophila. 3171 91
