Ameliorative influence of vildagliptin on genetic model of neurodegenerative diseases in Drosophila melanogaster

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Ishola, I.O.
Afolayan, O.
Akinleye, M.O.
Nwajei, W.I.
Adeyemi, O.O.
Mishra, R.K.
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Pharmaceutical Society of Nigeria
Background: Neurodegenerative disorders (ND) are characterized by progressive loss of selectively vulnerable populations of neurons, which contrasts with select static neuronal loss. Self-association of amyloid-beta (Aβ) or α-synuclein peptides into fibrils and/or plaque like aggregates causes neurotoxicity. Hence, identification of specific compounds that either inhibit the formation of Aβ or α syn-fibrils makes an appealing therapeutic strategy in the development of drugs. In the present study, we investigated the protective effect of vildagliptin (VDG) (oral hypoglycemic agent) on genetic models of ND in Drosophila melanogaster. Methods: The disease causing human Aβ42 peptide or α-syn was expressed pan-neuronally (elav GAL4) or dopamine neurons (DDC-GAL4) using the UAS-GAL4 system. Flies were either grown in food media with or without vildagliptin (1, 5, or 10µM). This was followed by fecundity, larva motility and negative geotaxis assay (climbing) as a measure of neurodegeneration. Results: Elav-Gal4<Aβ flies showed significant decrease in larva contraction and motility indicative of neurodegeneration. However, flies grown on vildaglitptin (VDG) showed dose-dependent and significant increase in larva motility in comparison with flies grown on food media only. Interestingly, the treatments did not affect fecundity when compared with normal food control. Moreover, flies grown on VDG showed no significant change in lifespan. DDC-GAL4<α-syn flies showed significant decrease in larva motility and climbing activity which was ameliorated by supplementation of flies food media with VDG suggestive of neuroprotective activity. Conclusion: Findings from this study showed that vildagliptin is a potential neuroprotective agent in genetic or familial forms of neurodegeneration.
Drosophila melanogaster , vildagliptin , UAS-GAL4 system , Alzheimer's disease , Parkinson disease , negative geotaxis
Ismail O. Ishola , Olasunmbo Afolayan , Moshood O. Akinleye , Winner Nwajei , Olufunmilayo O. Adeyemi , Rakesh K. Mishra. (2021).Ameliorative influence of vildagliptin on genetic model of neurodegenerative diseases in Drosophila melanogaster. THE NIGERIAN JOURNAL OF PHARMACY VOL.55,ISSUE(2):92-98.