High-Throughput and High-Content Screening for Huntington's Disease Therapeutics

2010 ◽  
pp. 121-145 ◽  
Author(s):  
Hemant Varma ◽  
Donald Lo ◽  
Brent Stockwell
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
High Throughput ◽  
High Content Screening

scholarly journals High-Throughput Multiplexed Quantitation of Protein Aggregation and Cytotoxicity in a Huntington’s Disease Model

2012 ◽  
Vol 6 ◽  
pp. 79-86 ◽  
Author(s):  
Steven A Titus ◽  
Noel Southall ◽  
Juan Marugan ◽  
Christopher P Austin ◽  
Wei Zheng
Keyword(s):  
Protein Aggregation ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
High Throughput ◽  
Disease Model

scholarly journals Modulating glial genes involved in synaptic function mitigates pathogenesis and behavioral deficits in a Drosophila model of Huntington’s Disease

2020 ◽  
Author(s):  
Tarik S. Onur ◽  
Andrew Laitman ◽  
He Zhao ◽  
Ryan Keyho ◽  
Hyemin Kim ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
High Throughput ◽  
Synaptic Function ◽  
Behavioral Deficits ◽  
Drosophila Model ◽  
Conserved Genes ◽  
Transcriptomic Changes ◽  
The Brain

AbstractMost research on neurodegenerative diseases has focused on neurons, yet glia help form and maintain the synapses whose loss is so prominent in these conditions. To investigate the contributions of glia to Huntington’s disease (HD), we studied transcriptomic changes in HD human, HD mice, and Drosophila expressing human mutant Huntingtin (mHTT) in either glia, neurons or both. A large portion of conserved genes are concordantly dysregulated across the three species; we tested these genes in a high-throughput behavioral assay and found that downregulation of genes involved in synapse assembly mitigated pathogenesis and behavioral deficits. To our surprise, mitigating glial pathogenesis by dNRXN3 knockdown was sufficient to improve the phenotype of flies expressing mHTT in neurons, suggesting that mHTT’s toxic effects in glia ramify throughout the brain. This supports a model in which dampening synaptic function is protective because it attenuates the excitotoxicity that characterizes HD.

scholarly journals Downregulation of glial genes involved in synaptic function mitigates Huntington's Disease pathogenesis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Tarik Seref Onur ◽  
Andrew Laitman ◽  
He Zhao ◽  
Ryan Keyho ◽  
Hyemin Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
High Throughput ◽  
Synaptic Function ◽  
Disease Pathogenesis ◽  
Behavioral Deficits ◽  
Conserved Genes ◽  
Gene Expression Alterations ◽  
The Brain

Most research on neurodegenerative diseases has focused on neurons, yet glia help form and maintain the synapses whose loss is so prominent in these conditions. To investigate the contributions of glia to Huntington's disease (HD), we profiled the gene expression alterations of Drosophila expressing human mutant Huntingtin (mHTT) in either glia or neurons and compared these changes to what is observed in HD human and HD mice striata. A large portion of conserved genes are concordantly dysregulated across the three species; we tested these genes in a high-throughput behavioral assay and found that downregulation of genes involved in synapse assembly mitigated pathogenesis and behavioral deficits. To our surprise, reducing dNRXN3 function in glia was sufficient to improve the phenotype of flies expressing mHTT in neurons, suggesting that mHTT's toxic effects in glia ramify throughout the brain. This supports a model in which dampening synaptic function is protective because it attenuates the excitotoxicity that characterizes HD.

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