Modeling Age‐Related Diseases in Drosophila: Can this Fly?

Michno, Kinga; Hoef, Diana van de; Wu, Huadong; Boulianne, Gabrielle L.

doi:10.1016/s0070-2153(05)71006-1

Cited by 13 publications

(14 citation statements)

References 105 publications

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“…This comes, in part, from estimates of 75% of all human disease genes have related sequences in Drosophila (Bier, 2005). Drosophila models have been developed for cancer, cardiac disease, and several neurodegenerative diseases such as Parkinson's disease, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (reviewed in Bier and Bodmer, 2004;Bier, 2005;Michno et al, 2005;Vidal and Cagan, 2006). Here we review Drosophila modeling of human seizure disorders.…”

Section: Introductionmentioning

confidence: 99%

From bench to drug: Human seizure modeling using Drosophila

Song

Tanouye

2008

Progress in Neurobiology

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Studies of human seizure disorders have revealed that susceptibility to seizures is greatly influenced by genetic factors. In addition to causing epilepsy, genetic factors can suppress seizures and epileptogenesis. Examination of seizure-suppressor genes is challenging in humans. However, such genes are readily identified and analyzed in a Drosophila animal model of epilepsy. In this article, the epilepsy phenotype of Drosophila seizure-sensitive mutants is reviewed. A novel class of genes called seizure-suppressors is described. Mutations defining suppressors revert the "epilepsy" phenotype of neurological mutants. We conclude this review with particular discussion of a seizure-suppressor gene encoding DNA topoisomerase I (top1). Mutations of top1 are especially effective at reverting the seizure-sensitive phenotype of Drosophila epilepsy mutants. In addition, an unexpected class of anti-epileptic drugs has been identified. These are DNA topoisomerase I inhibitors such as camptothecin and its derivatives; several candidates are comparable or perhaps better than traditional anti-epileptic drugs such as valproate at reducing seizures in Drosophila drug-feeding experiments.

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Section: Introductionmentioning

confidence: 99%

From bench to drug: Human seizure modeling using Drosophila

Song

Tanouye

2008

Progress in Neurobiology

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“…Indeed, the genetic advantages of these Drosophila models have been used to look for genetic interactions and intervention therapeutics (Michno et al, 2005). Of note is the demonstration that expression of human DEtorsinA leads to dystonic like behaviors in the fly (Koh et al, 2004), suggesting that an analysis of torsin function in the fly will be insightful into understanding torsin biology.…”

Section: Introductionmentioning

confidence: 99%

Down‐regulation of torp4a, encoding the Drosophila homologue of torsinA, results in increased neuronal degeneration

Muraro

Moffat

2006

J. Neurobiol.

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Early-onset torsion dystonia is a dominant motor disorder linked to mutations in torsinA. TorsinA is weakly related to a superfamily of chaperone-like proteins. The function of the torsin group remains largely unknown. Here we use RNAi and over-expression to analyze the function of torp4a, the only Drosophila torsin. Targeted down-regulation in the eye causes progressive degeneration of the retina. Conversely, over-expression of torp4a protects from age-related degeneration. In the retinas of young animals, a correlation with the lysosome-related organelle, the pigment granule, is also observed. Lowering torp4a causes an increase in pigment granules, while over-expression causes loss of granules. We have performed a screen for genetic interactors of torp4a identifying a number mutants, including two members of the AP-3 complex. Other genetic interactors found included genes related to actin and myosin function. Our findings implicate the Drosophila torsin, torp4a, to function with molecules consistent with already predicted roles in the endoplasmic reticulum/nuclear envelope compartment, and have identified potential new interactions with AP-3 like components.

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“…Working with fruit flies is very convenient in this sense, as it is inexpensive to keep a fruit fly stock. Fruit flies require little care, labor or complicated high-tech devices (Bilen and Bonini 2005;Michno et al 2005). They also needed an animal model with a short life span so as to overrule the failed hypotheses quickly.…”

Section: Fly Modelmentioning

confidence: 99%