Understanding Neurodegeneration and Neuroprotection Through Genetic Screens in Drosophila

Mandya, Aishwarya S; Cheramangalam, Rajit Narayanan; Jaiswal, Manish

doi:10.1007/978-981-13-2218-1_3

Cited by 2 publications

(1 citation statement)

References 227 publications

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“…Drosophila melanogaster have been used extensively to model polyQ diseases and led to numerous discoveries that have profoundly changed our understanding of many diseases [4][5][6] . Various different constructs have been used to introduce polyQ repeats into the fly including N-terminal fragments of huntingtin 7,8 , C-terminal fragments of ataxin-3 9 , naked polyQ tracts 10 , epitope-tagged polyQ tracts 10,11 , and the full-length ataxin-1 gene 12 .…”

Section: Introductionmentioning

confidence: 99%

Juvenile and adult expression of polyglutamine expandedhuntingtinproduce distinct aggregate distributions inDrosophilamuscle

Barwell

Raina

Page

et al. 2023

Preprint

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While Huntington's disease (HD) is widely recognized as a disease affecting the nervous system, much evidence has accumulated to suggest peripheral or non-neuronal tissues are affected as well. Here, we utilize the UAS/GAL4 system to express a pathogenic HD construct in the muscle of the fly, and characterize the effects. We observe detrimental phenotypes such as reduced lifespan, decreased locomotion, and accumulation of protein aggregates. Strikingly, depending on the GAL4 driver used to express the construct we saw different aggregate distributions and severity of phenotypes. These different aggregate distributions were found to be dependent on expression level and the timing of expression. Hsp70, a well-documented suppressor of polyglutamine aggregates, was found to strongly reduce the accumulation of aggregates in the eye, but in the muscle it did not prevent the reduction of the lifespan. Therefore, the molecular mechanisms underlying the detrimental effects of aggregates in the muscle are distinct from the nervous system.

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Section: Introductionmentioning

confidence: 99%

Juvenile and adult expression of polyglutamine expandedhuntingtinproduce distinct aggregate distributions inDrosophilamuscle

Barwell

Raina

Page

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Juvenile and adult expression of polyglutamine expanded huntingtin produce distinct aggregate distributions in Drosophila muscle

Barwell

Raina

Page

et al. 2023

Human Molecular Genetics

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While Huntington’s disease (HD) is widely recognized as a disease affecting the nervous system, much evidence has accumulated to suggest peripheral or non-neuronal tissues are affected as well. Here, we utilize the UAS/GAL4 system to express a pathogenic HD construct in the muscle of the fly, and characterize the effects. We observe detrimental phenotypes such as reduced lifespan, decreased locomotion, and accumulation of protein aggregates. Strikingly, depending on the GAL4 driver used to express the construct we saw different aggregate distributions and severity of phenotypes. These different aggregate distributions were found to be dependent on expression level and the timing of expression. Hsp70, a well-documented suppressor of polyglutamine aggregates, was found to strongly reduce the accumulation of aggregates in the eye, but in the muscle it did not prevent the reduction of the lifespan. Therefore, the molecular mechanisms underlying the detrimental effects of aggregates in the muscle are distinct from the nervous system.

show abstract

Understanding Neurodegeneration and Neuroprotection Through Genetic Screens in Drosophila

Cited by 2 publications

References 227 publications

Juvenile and adult expression of polyglutamine expandedhuntingtinproduce distinct aggregate distributions inDrosophilamuscle

Juvenile and adult expression of polyglutamine expandedhuntingtinproduce distinct aggregate distributions inDrosophilamuscle

Juvenile and adult expression of polyglutamine expanded huntingtin produce distinct aggregate distributions in Drosophila muscle

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