Dataset Information

Dataset on the effect of Rubicon overexpression on polyglutamine-induced locomotor dysfunction in Drosophila.

ABSTRACT: The accumulation of pathogenic misfolded proteins is believed to be a common mechanism of generation of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and polyglutamine (polyQ) diseases. The autophagy-lysosome degradation system has been considered as a potential therapeutic target against these disorders, as it is able to degrade large protein aggregates. Previously, we focused on Rubicon, a negative regulator of autophagy, and demonstrated that knockdown of the Drosophila homolog of Rubicon (dRubicon) suppressed locomotor dysfunction in a fly model of polyQ disease. This suppression was associated with increased autophagic activity and a marked reduction in the number of polyQ inclusion bodies [1]. We generated transgenic fly lines expressing hemagglutinin-tagged dRubicon wild-type (WT) or dRubicon in which the RUN [after RPIP8 (RaP2 interacting protein 8), UNC-14 and NESCA (new molecule containing SH3 at the carboxyl-terminus)] domain was deleted (ΔRUN). We provide data regarding the effect of WT and ΔRUN dRubicon co-expression on polyQ-induced locomotor dysfunction in Drosophila.

SUBMITTER: Oba M

PROVIDER: S-EPMC8220321 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundRodent kindling induced by PTZ is a widely used model of epileptogenesis and AED testing. Overlapping pathophysiological mechanisms may underlie epileptogenesis and other neuropsychiatric conditions. Besides epilepsy, AEDs are widely used in treating various neuropsychiatric disorders. Mechanisms of AEDs' long term action in these disorders are poorly understood. We describe here a Drosophila systems model of PTZ induced locomotor plasticity that is responsive to AEDs.ResultsWe empirically determined a regime in which seven days of PTZ treatment and seven days of subsequent PTZ discontinuation respectively cause a decrease and an increase in climbing speed of Drosophila adults. Concomitant treatment with NaVP and LEV, not ETH, GBP and VGB, suppressed the development of locomotor deficit at the end of chronic PTZ phase. Concomitant LEV also ameliorated locomotor alteration that develops after PTZ withdrawal. Time series of microarray expression profiles of heads of flies treated with PTZ for 12 hrs (beginning phase), two days (latent phase) and seven days (behaviorally expressive phase) showed only down-, not up-, regulation of genes; expression of 23, 2439 and 265 genes were downregulated, in that order. GO biological process enrichment analysis showed downregulation of transcription, neuron morphogenesis during differentiation, synaptic transmission, regulation of neurotransmitter levels, neurogenesis, axonogenesis, protein modification, axon guidance, actin filament organization etc. in the latent phase and of glutamate metabolism, cell communication etc. in the expressive phase. Proteomic interactome based analysis provided further directionality to these events. Pathway overrepresentation analysis showed enrichment of Wnt signaling and other associated pathways in genes downregulated by PTZ. Mining of available transcriptomic and proteomic data pertaining to established rodent models of epilepsy and human epileptic patients showed overrepresentation of epilepsy associated genes in our PTZ regulated set.ConclusionSystems biology ultimately aims at delineating and comprehending the functioning of complex biological systems in such details that predictive models of human diseases could be developed. Due to immense complexity of higher organisms, systems biology approaches are however currently focused on simpler organisms. Amenable to modeling, our model offers a unique opportunity to further dissect epileptogenesis-like plasticity and to unravel mechanisms of long-term action of AEDs relevant in neuropsychiatric disorders.

Dataset Information

Dataset on the effect of Rubicon overexpression on polyglutamine-induced locomotor dysfunction in Drosophila.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets