Flies with Parkinson's disease

Vanhauwaert, Roeland; Verstreken, Patrik

doi:10.1016/j.expneurol.2015.02.020

Cited by 31 publications

(15 citation statements)

References 201 publications

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“…Moreover, its genome sequence has been available since 2000 (Myers, Sutton, Delcher, Dew & Fasulo, 2000) and can be easily manipulated through the use of various genetic tools, including transposable P elements, homologous recombination or the GAL4/UAS system that permits expression of specific transgenes in a tissue-or cell-specific manner (Brand & Perrimon, 1993). Interestingly, Drosophila has many orthologs to PD-related human genes, including DJ-1, Parkin, LRRK2 and PINK1, with the exception of αsyn (Vanhauwaert & Verstreken, 2015), which makes this organism an attractive tool to study pathological mechanisms of PD. Drosophila has a complex nervous system.…”

Section: Flies (Drosophila Melanogaster)mentioning

confidence: 99%

Genetically engineered animal models of Parkinson's disease: From worm to rodent

Breger

Fuzzati-Armentero²

2018

Eur J of Neuroscience

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Parkinson's disease (PD) is a progressive neurological disorder characterised by aberrant accumulation of insoluble proteins, including alpha‐synuclein, and a loss of dopaminergic neurons in the substantia nigra. The extended neurodegeneration leads to a drop of striatal dopamine levels responsible for disabling motor and non‐motor impairments. Although the causes of the disease remain unclear, it is well accepted among the scientific community that the disorder may also have a genetic component. For that reason, the number of genetically engineered animal models has greatly increased over the past two decades, ranging from invertebrates to more complex organisms such as mice and rats. This trend is growing as new genetic variants associated with the disease are discovered. The EU Joint Programme – Neurodegenerative Disease Research (JPND) has promoted the creation of an online database aiming at summarising the different features of experimental models of Parkinson's disease. This review discusses available genetic models of PD and the extent to which they adequately mirror the human pathology and reflects on future development and uses of genetically engineered experimental models for the study of PD.

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Section: Flies (Drosophila Melanogaster)mentioning

confidence: 99%

Genetically engineered animal models of Parkinson's disease: From worm to rodent

Breger

Fuzzati-Armentero²

2018

Eur J of Neuroscience

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“…melanogaster is widely used test-organism while investigating pathogenesis of Parkinson's disease [8,9]. So, it is a good model to study effects of antiparkinsonian chemicals [10].…”

Section: Dmentioning

confidence: 99%

The action of monoterpenoids with promising antiparkinsonian activity on fertility of Drosophila melanogaster

Trushin¹,

Khamidullina²,

Ardashov³

et al. 2017

mpj

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Adequate treatment of Parkinson's disease is an important medical issue. Patients are suffered from numerous side effects of the widely used drugs. It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl) cyclohex-3-ene-1,2-diol and its diacetate demonstrate high antiparkinsonian activity in some animal models. At the same time, their genetic safety was not studied yet. The aim of this research was to investigate the effect of these compounds with antiparkinsonian activities on reproduction of D. melanogaster.Over 4000 of fruitflies cultivated under the action of these compounds were analyzed. It was found that the chemicals did not provoke genetic mutations or alter reproduction of D. melanogaster. The possible explanations for the detected phenomena are provided. It was found that the compounds do not affect fertility in Drosophila.. Key words:Parkinson's disease; fertility; drosophila; (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol; acetate; terpene.

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“…A majority of PD cases are idiopathic but the emergence of familial cases led to the identification and study of genes that are highly associated with PD [6, 7]. The understanding and exploitation of the genetic basis of PD has revealed over 20 genes that are implicated in PD pathogenesis [8], and highlighted the complexity of this neurodegenerative disease.…”

Section: Introductionmentioning

confidence: 99%

A loss of Pdxk model of Parkinson disease in Drosophila can be suppressed by Buffy

M’Angale

Staveley

2017

BMC Res Notes

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BackgroundThe identification of a DNA variant in pyridoxal kinase (Pdxk) associated with increased risk to Parkinson disease (PD) gene led us to study the inhibition of this gene in the Dopa decarboxylase (Ddc)-expressing neurons of the well-studied model organism Drosophila melanogaster. The multitude of biological functions attributable to the vitamers catalysed by this kinase reveal an overabundance of possible links to PD, that include dopamine synthesis, antioxidant activity and mitochondrial function. Drosophila possesses a single homologue of Pdxk and we used RNA interference to inhibit the activity of this kinase in the Ddc-Gal4-expressing neurons. We further investigated any association between this enhanced disease risk gene with the established PD model induced by expression of α-synuclein in the same neurons. We relied on the pro-survival functions of Buffy, an anti-apoptotic Bcl-2 homologue, to rescue the Pdxk-induced phenotypes.ResultsTo drive the expression of Pdxk RNA interference in DA neurons of Drosophila, we used Ddc-Gal4 which drives expression in both dopaminergic and serotonergic neurons, to result in decreased longevity and compromised climbing ability, phenotypes that are strongly associated with Drosophila models of PD. The inhibition of Pdxk in the α-synuclein-induced Drosophila model of PD did not alter longevity and climbing ability of these flies. It has been previously shown that deficiency in vitamers lead to mitochondrial dysfunction and neuronal decay, therefore, co-expression of Pdxk-RNAi with the sole pro-survival Bcl-2 homologue Buffy in the Ddc-Gal4-expressing neurons, resulted in increased survival and a restored climbing ability. In a similar manner, when we inhibited Pdxk in the developing eye using GMR-Gal4, we found that there was a decrease in the number of ommatidia and the disruption of the ommatidial array was more pronounced. When Pdxk was inhibited with the α-synuclein-induced developmental eye defects, the eye phenotypes were unaltered. Interestingly co-expression with Buffy restored ommatidia number and decreased the severity of disruption of the ommatidial array.ConclusionsThough Pdxk is not a confirmed Parkinson disease gene, the inhibition of this kinase recapitulated the PD-like symptoms of decreased lifespan and loss of locomotor function, possibly producing a new model of PD.

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Flies with Parkinson's disease

Cited by 31 publications

References 201 publications

Genetically engineered animal models of Parkinson's disease: From worm to rodent

Genetically engineered animal models of Parkinson's disease: From worm to rodent

The action of monoterpenoids with promising antiparkinsonian activity on fertility of Drosophila melanogaster

A loss of Pdxk model of Parkinson disease in Drosophila can be suppressed by Buffy

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