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Review
. 2018 Jul 7;19(7):1989.
doi: 10.3390/ijms19071989.

Impact of Drosophila Models in the Study and Treatment of Friedreich's Ataxia

Véronique Monnier  1 , Jose Vicente Llorens  2 , Juan Antonio Navarro  3
Affiliations
Review

Impact of Drosophila Models in the Study and Treatment of Friedreich's Ataxia

Véronique Monnier et al. Int J Mol Sci. .

Abstract

Drosophila melanogaster has been for over a century the model of choice of several neurobiologists to decipher the formation and development of the nervous system as well as to mirror the pathophysiological conditions of many human neurodegenerative diseases. The rare disease Friedreich’s ataxia (FRDA) is not an exception. Since the isolation of the responsible gene more than two decades ago, the analysis of the fly orthologue has proven to be an excellent avenue to understand the development and progression of the disease, to unravel pivotal mechanisms underpinning the pathology and to identify genes and molecules that might well be either disease biomarkers or promising targets for therapeutic interventions. In this review, we aim to summarize the collection of findings provided by the Drosophila models but also to go one step beyond and propose the implications of these discoveries for the study and cure of this disorder. We will present the physiological, cellular and molecular phenotypes described in the fly, highlighting those that have given insight into the pathology and we will show how the ability of Drosophila to perform genetic and pharmacological screens has provided valuable information that is not easily within reach of other cellular or mammalian models.

Keywords: Drosophila melanogaster; Friedreich’s ataxia; drug screens; endoplasmic reticulum; frataxin; genetic screens; iron; lipid metabolism; metal homeostasis; oxidative stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Graphic summary of molecular defects and rescues described in Drosophila melanogaster models of frataxin-deficiency in relation to Fe–S clusters generation and mitochondrial function.
Figure 2
Figure 2
Graphic summary of molecular defects and rescues described in Drosophila melanogaster models of frataxin-deficiency in relation to iron metabolism and homeostasis of other metals.
Figure 3
Figure 3
Graphic summary of molecular defects and rescues described in Drosophila melanogaster models of frataxin-deficiency in relation to oxidative stress and lipid metabolism.
Figure 4
Figure 4
Graphic summary of molecular defects and rescues described in Drosophila melanogaster models of frataxin-deficiency in relation to the cellular mitochondrial network.
See this image and copyright information in PMC

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