Ameliorative influence of atorvastatin in transgenic Drosophila Melanogaster model of neurodegenerative diseases

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 effiffifficient treatments are available. The fruit flfly, 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 specifific promoter; embryonic lethal abnormal visual system GAL4 (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 flflies were was either maintained on media supplemented with vehicle or atorvastatin (85, 170 or 340µM; HMG-CoA reductase inhibitor – antihyperlipidemic drug). The effffect of treatments on larva motility, climbing activity, fecundity and lifespan were recorded. Results: Supplementation of flfly media with difffferent concentration of atorvastatin ameliorated the deficits in larva motility and climbing activity. Moreover, supplementation of flfly 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.