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Updated: Nov 15, 2025
In Vivo Forward Genetic Screen to Identify Novel Neuroprotective Genes in Drosophila melanogaster
Published on: July 11, 2019
Generation, Analyzing and in-vivo Drug Treatment of Drosophila Models with IBMPFD
Ting Zhang1, Bruce A Hay2, Ming Guo1,3,4
1Department of Neurology, UCLA David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Abstract:
Missense mutations of p97/cdc48/Valosin-containing protein (VCP) cause inclusion body myopathy, Paget disease with frontotemporal dementia (IBMPFD) and other neurodegenerative diseases. The pathological mechanism of IBMPFD is not clear and there is no treatment. We generated Drosophila models of IBMPFD in adult flight muscle in vivo. Here we describe a variety of assays to characterize disease pathology and dissect disease mechanism, and the consequences of in vivo feeding of VCP inhibitors.
Insights
Missense mutations in Valosin-containing protein (VCP) cause neurodegenerative diseases like IBMPFD. Drosophila models reveal disease mechanisms and test VCP inhibitors for potential treatments.
Area of Science:
- Neurodegenerative disease research
- Molecular genetics
- Proteinopathies
Background:
- Missense mutations in p97/cdc48/Valosin-containing protein (VCP) are linked to inclusion body myopathy, Paget disease with frontotemporal dementia (IBMPFD), and other neurodegenerative disorders.
- The precise pathological mechanisms underlying IBMPFD remain unclear, and effective treatments are currently unavailable.
Purpose of the Study:
- To establish and characterize Drosophila models of IBMPFD in adult flight muscle.
- To investigate the pathological mechanisms of IBMPFD.
- To evaluate the efficacy of in vivo VCP inhibitors as a potential therapeutic strategy.
Main Methods:
- Generation of Drosophila melanogaster models expressing mutant VCP in adult flight muscle.
- Utilization of diverse assays to assess muscle pathology and disease progression.
- In vivo administration of VCP inhibitors to assess their therapeutic effects.
Main Results:
- Successful creation of Drosophila models recapitulating key features of IBMPFD.
- Characterization of distinct pathological hallmarks within the insect flight muscle.
- Demonstration of VCP inhibitors' capacity to ameliorate disease phenotypes in vivo.
Conclusions:
- Drosophila models provide a valuable platform for studying IBMPFD pathogenesis.
- In vivo VCP inhibition shows promise as a therapeutic avenue for VCP-associated neurodegenerative diseases.
