Screening of coumarin derivatives as a potential Alzheimer’s Disease treatment drugs on Drosophila melanogaster
Keywords:
Alzheimer's disease, amyloid beta, Drosophila melanogasterAbstract
Alzheimer's disease (AD) stands as the most prevalent form of neurodegenerative ailment worldwide, characterized by the accumulation of amyloid beta (Aβ) plaques. Unfortunately, there is currently no effective cure for this condition. To investigate potential treatment options, researchers have turned to Drosophila melanogaster as an ideal animal model for studying AD. In this context, coumarin, a naturally occurring phytochemical initially discovered in tonka bean, and its derivatives have garnered significant attention for their diverse beneficial biological properties. The present study aimed to explore the efficacy of coumarin derivatives in mitigating the adverse effects of Aβ aggregation. Using the Drosophila model expressing human Aβ42, researchers observed a rough eye phenotype (REP) and decreased lifespan. To evaluate the neuroprotective effects of coumarin derivatives, the treated groups' eye morphology was compared with both positive and negative control groups. Encouragingly, the group treated with S5-44 exhibited the most favourable eye morphology, closely resembling that of the positive control group compared to other coumarin derivatives. Moreover, the group treated with S3-18 displayed a longer lifespan in comparison to the negative control group. In summary, most coumarin derivatives utilized in this study partially restored the REP, while one derivative even extended the lifespan of Drosophila. These promising findings suggest that coumarin derivatives have the potential to serve as neuroprotective drugs for the treatment of AD. Further research and development in this area may open new avenues for combating this debilitating disease.
References
Bass, T. M., Grandison, R. C., Wong, R., Martinez, P., Partridge, L., & Piper, M. D. (2007). Optimization of dietary restriction protocols in Drosophila. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 62(10), 1071-1081.
Botas, J. (2007). Drosophila researchers focus on human disease. Nat Genet, 39(5), 589-591.
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006). Alzheimer's disease. Lancet (London, England), 368(9533), 387–403.
Fernandez-Funez, P., Sanchez-Garcia, J. & Rincon-Limas, D. (2013) Unraveling the basis of neurodegeneration using the Drosophila eye. In: Molecular genetics of axial patterning, growth and disease in the Drosophila eye (A. Singh & M. Kango-Singh, eds.), pp 271–293. New York: Springer.
Hamulakova, S., Janovec, L., Soukup, O., Jun, D., & Kuca, K. (2017). Synthesis, in vitro acetylcholinesterase inhibitory activity and molecular docking of new acridine-coumarin hybrids. Int J Biol Macromol, 104(Pt A), 333-338.
Hardy, J. (2009). The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. Journal of Neurochemistry, 110(4), 1129-1134.
Hardy, J., & Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science, 297(5580), 353-356.
Huang, M., Xie, S. S., Jiang, N., Lan, J. S., Kong, L. Y., & Wang, X. B. (2015). Multifunctional coumarin derivatives: monoamine oxidase B (MAO-B) inhibition, anti-beta-amyloid (Abeta) aggregation and metal chelation properties against Alzheimer's disease. Bioorg Med Chem Lett, 25(3), 508-513.
Iijima, K., Liu, H. P., Chiang, A. S., Hearn, S. A., Konsolaki, M., & Zhong, Y. (2004). Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer's disease. Proc Natl Acad Sci U S A, 101(17), 6623-6628.
Lee, K. P., Simpson, S. J., Clissold, F. J., Brooks, R., Ballard, J. W. O., Taylor, P. W., Raubenheimer, D. (2008). Lifespan and reproduction in Drosophila: new insights from nutritional geometry. Proc Natl Acad Sci USA, 105(7), 2498-2503.
Lenz, S., Karsten, P., Schulz, J. B., & Voigt, A. (2013). Drosophila as a screening tool to study human neurodegenerative diseases. J Neurochem, 127(4), 453-460.
Lin, M. T., & Beal, M. F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 443(7113), 787-795.
Pandey, U. B., & Nichols, C. D. (2011). Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev, 63(2), 411-436.
Rubin, G. M. (2000). Biological annotation of the Drosophila genome sequence. Paper presented at the Novartis Foundation symposium.
Sarkar, A., Irwin, M., Singh, A., Riccetti, M., & Singh, A. (2016). Alzheimer's disease: the silver tsunami of the 21(st) century. Neural Regeneration Research, 11(5), 693-697.
Selkoe, D. J., & Hardy, J. (2016). The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med, 8(6), 595-608.
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011). Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med, 1(1), a006189.
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Selkoe, D. J. (2008). Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med, 14(8), 837-842.
Stocker, H., & Gallant, P. (2008). Getting started: an overview on raising and handling Drosophila. Methods Mol Biol, 420, 27-44.
Tanzi, R. E., & Bertram, L. (2005). Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell, 120(4), 545-555.
Tare, M., Modi, R. M., Nainaparampil, J. J., Puli, O. R., Bedi, S., Fernandez-Funez, P., Singh, A. (2011). Activation of JNK signaling mediates amyloid-ss-dependent cell death. PLoS One, 6(9), e24361.
Wang, J., Gu, B. J., Masters, C. L., & Wang, Y. J. (2017). A systemic view of Alzheimer disease - insights from amyloid-beta metabolism beyond the brain. Nat Rev Neurol, 13(10), 612-623.
William, W. J., Carvalho, G. B., Mak, E. M., Noelle, N., Fang, A. Y., Liong, J. C., Benzer, S. (2007). Prandiology of Drosophila and the CAFE assay. Proceedings of the National Academy of Sciences, 104(20), 8253-8256.
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Zetterberg, H. (2016). Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol, 15(5), 455-532.
Wittmann, C. W., Wszolek, M. F., Shulman, J. M., Salvaterra, P. M., Lewis, J., Hutton, M., & Feany, M. B. (2001). Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science, 293(5530), 711-714.
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