Ameliorative influence of atorvastatin in transgenic Drosophila Melanogaster model of neurodegenerative diseases
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Date
2021-03-31
Authors
Ishola, I.O.
Badru, W.A.
Ofi, E.O.
Akinleye, M.O.
Adeyemi, O.O.
Journal Title
Journal ISSN
Volume Title
Publisher
Pharmaceutical Society of Nigeria
Abstract
Background: The common features in the pathogenesis of Alzheimer's disease (AD) and
Parkinson disease (PD) (two most common neurodegenerative diseases) are chronic and
progressive aggregation and accumulation of misfolded proteins (amyloid-beta and tau proteins in
AD as well as α-synuclein in PD) leading to the destruction of vulnerable neurons and synaptic
connections and ultimately neuronal cell death brain mass loss. Despite our knowledge of the
molecular mechanisms implicated in AD and PD pathogenesis and primary target of therapeutic
intervention being the misfolded protein aggregates, no efficient treatments are available. The fruit
fly, Drosophila melanogaster (Drosophila), is a valuable model organism for neurodegenerative
disease owing to its short lifespan and plethora of genetic tools for exquisite targeted manipulation
of the genome. Thus, in this study the protective action of atorvastatin on genetic model of AD and
PD in mice.
Methods: To model PD and AD in Drosophila, the bipartite system of GAL4 transcriptional
activator was placed under a cell-type specific promoter; embryonic lethal abnormal visual systemGAL4 (ELAV-GAL4) or dopa decarboxylase (Ddc-GAL4) for expression of amyloid-beta (Aβ42)
or α-synuclein, respectively, under the control of the upstream activating sequence (UAS) in
Drosophila. The flies were was either maintained on media supplemented with vehicle or
atorvastatin (85, 170 or 340µM; HMG-CoA reductase inhibitor – antihyperlipidemic drug). The
effect of treatments on larva motility, climbing activity, fecundity and lifespan were recorded.
Results: Supplementation of fly media with different concentration of atorvastatin ameliorated the
deficits in larva motility and climbing activity. Moreover, supplementation of fly media with
atorvastatin prolonged the survival of drosophila but atorvastatin (384µM) reduced fecundity.
Conclusion: Findings from this study showed that atorvastatin improved spontaneous motor
activity and prolonged lifespan in Drosophila possibly through reduction of misfolded protein
aggregates
Description
Scholarly article
Keywords
α-synuclein , Aβ42 , UAS-GAL4 system , lifespan , fecundity , Research Subject Categories::PHARMACY
Citation
Ismail O. Ishola , Wasiu A. Badru , Emmanuel O. Ofi , Moshood O. Akinleye , Olufunmilayo O. Adeyemi. (2021). Ameliorative influence of atorvastatin in transgenic Drosophila Melanogaster model of neurodegenerative diseases. THE NIGERIAN JOURNAL OF PHARMACY VOL. 55 ISSUE (1):40-45