Ameliorative influence of vildagliptin on genetic model of neurodegenerative diseases in Drosophila melanogaster
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Date
2021-09-30
Authors
Ishola, I.O.
Afolayan, O.
Akinleye, M.O.
Nwajei, W.I.
Adeyemi, O.O.
Mishra, R.K.
Journal Title
Journal ISSN
Volume Title
Publisher
Pharmaceutical Society of Nigeria
Abstract
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.
Description
Keywords
Drosophila melanogaster , vildagliptin , UAS-GAL4 system , Alzheimer's disease , Parkinson disease , negative geotaxis
Citation
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.