Dissecting Pathogenetic Mechanisms and Therapeutic Strategies in Drosophila Models of Myotonic Dystrophy Type 1
Abstract
:1. Introduction
2. DM1 Pathogenesis
3. Drosophila Could Serve as a Model Organism for DM1
4. Identification of New Mechanisms Underlying DM1 Using Drosophila Models
5. Discovering Potential Gene and Drug-Based Therapeutic Strategies Using Fly DM1 Models
6. Conclusion and Remarks
Author Contributions
Funding
Conflicts of Interest
References
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Screen | Identified Drug | Drosophila Model | Phenotype/Mode of Action | Ref. |
---|---|---|---|---|
Genetic Modifier Screening | Suppressors: cnc, Nurf-38, foi, coro, csk, spinster; Enhancers: seven up, viking, cg4589 | 480 interrupted CTG | CUG-induced rough-eye phenotype | [37] |
Smaug | 480 interrupted CTG | Restoration of translational activity of CELF1/Bru-3, rescue of CUG-induced myopathy (prevents muscle wasting/restore muscle function) | [60] | |
apoptosis/autophagy inhibitors (overexpression of DIAP1, mTOR or muscleblind) | 480 interrupted CTG | Rescue of the muscle-loss phenotype (atrophy) | [61] | |
Drug Screening | Non-steroidal anti-inflammatory agents, dopamine receptors and monoamine uptake inhibitors, Na+ and Ca2+ metabolism, Muscarinic, cholinergic and histamine receptors inhibitors | 480 interrupted CTG) | Suppression of CUG-induced lethality | [37] |
d-amino acid hexapeptide (ABP1) | 480 interrupted CTG | Biding to CUG repeats, elimination of CUG-RNA hairpin formation, suppression of CUG-induced lethality and muscle degeneration | [66] | |
Ligand 3 | 480 interrupted CTG | Inhibition of MBNL1-CUG interaction, reduction of ribonuclear foci, partial rescue of misregulated splicing and degenerative phenotypes | [67] | |
Ligand 2a | 480 interrupted CTG | Inhibition of MBNL1-CUG interaction, reduction of ribonuclear foci, amelioration of adult external eye degeneration and larval crawling defect | [68] | |
Pentamidine | 250 pure CTG repeats | Inhibition of MBNL1-CUG interaction, reduction of ribonuclear foci, rescue of heart arrhythmicity and contractility, fly survival | [46] | |
Daunorubicin hydrochloride | 250 pure CTG repeats | Inhibition of MBNL1-CUG interaction, rescue of Mbl-dependent missplicing/cardiac function recovery (systolic interval and diastolic interval), fly survival | [29] |
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Souidi, A.; Zmojdzian, M.; Jagla, K. Dissecting Pathogenetic Mechanisms and Therapeutic Strategies in Drosophila Models of Myotonic Dystrophy Type 1. Int. J. Mol. Sci. 2018, 19, 4104. https://doi.org/10.3390/ijms19124104
Souidi A, Zmojdzian M, Jagla K. Dissecting Pathogenetic Mechanisms and Therapeutic Strategies in Drosophila Models of Myotonic Dystrophy Type 1. International Journal of Molecular Sciences. 2018; 19(12):4104. https://doi.org/10.3390/ijms19124104
Chicago/Turabian StyleSouidi, Anissa, Monika Zmojdzian, and Krzysztof Jagla. 2018. "Dissecting Pathogenetic Mechanisms and Therapeutic Strategies in Drosophila Models of Myotonic Dystrophy Type 1" International Journal of Molecular Sciences 19, no. 12: 4104. https://doi.org/10.3390/ijms19124104