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Targeted Downregulation of dMyc Suppresses Pathogenesis of Human Neuronal Tauopathies in Drosophila by Limiting Heterochromatin Relaxation and Tau Hyperphosphorylation.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2017 May; Vol. 54 (4), pp. 2706-2719. Date of Electronic Publication: 2016 Mar 21. - Publication Year :
- 2017
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Abstract
- Human tauopathies such as Alzheimer's Disease (AD), frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick's disease etc., are a group of neurodegenerative diseases which are characterized by abnormal hyperphosphorylation of tau that leads to formation of neurofibrillary tangles. Recapitulating several features of human neurodegenerative disorders, the Drosophila tauopathy model displays compromised lifespan, locomotor function impairment, and brain vacuolization in adult brain which is progressive and age dependent. Here, we demonstrate that tissue-specific downregulation of the Drosophila homolog of human c-myc proto-oncogene (dMyc) suppresses tau-mediated morphological and functional deficits by reducing abnormal tau hyperphosphorylation and restoring the heterochromatin loss. Our studies show for the first time that the inherent chromatin remodeling ability of myc proto-oncogenes could be exploited to limit the pathogenesis of human neuronal tauopathies in the Drosophila disease model. Interestingly, recent reports on successful uses of some anti-cancer drugs against Alzheimer's and Parkinson's diseases in clinical trials and animal models strongly support our findings and proposed possibility.
- Subjects :
- Acetylation
Animals
Animals, Genetically Modified
Apoptosis
Brain pathology
Chromatin Assembly and Disassembly
Eye metabolism
Eye ultrastructure
Histones metabolism
Humans
Nerve Degeneration metabolism
Nerve Degeneration pathology
Neurons pathology
Phosphorylation
Proto-Oncogene Mas
Reactive Oxygen Species metabolism
Tauopathies pathology
DNA-Binding Proteins metabolism
Down-Regulation
Drosophila Proteins metabolism
Drosophila melanogaster metabolism
Heterochromatin metabolism
Neurons metabolism
Tauopathies metabolism
Transcription Factors metabolism
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 54
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 27000837
- Full Text :
- https://doi.org/10.1007/s12035-016-9858-6