ArticleNeurobiology of disease2025
Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease.
Article in Neurobiology of disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Disrupted Transcriptional Networks in Mammalian Cells Stably Over-Expressing Pathogenic Atrophin-1.Journal of neuroscience research · 2025Article
- Wings of Discovery: UsingCells · 2025Review
- Disrupted Transcriptional Networks by Mutant Atrophin-1 in a Cell Culture Model of Dentatorubral-Pallidoluysian Atrophy.bioRxiv : the preprint server for biology · 2025Article
- Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinson's Disease.NPJ Parkinson's disease · 2025Article
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10 authors.
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Abstract
Dentatorubral-pallidoluysian atrophy (DRPLA) is a neurodegenerative disorder that presents with ataxia, dementia and epilepsy. As a member of the polyglutamine family of diseases, DRPLA is caused by abnormal CAG triplet expansion beyond 48 repeats in the protein-coding region of ATROPHIN 1 (ATN1), a transcriptional co-repressor. To better understand DRPLA, we generated new Drosophila lines that can be induced to express full-length, human ATN1 with a normal (Q7) or pathogenic (Q88) repeat in a variety of cells, including neuronal, glial or any other type of tissue. Expression of ATN1 is toxic, with the polyglutamine-expanded version being consistently more problematic than wild-type ATN1. Fly motility, longevity and internal structures are negatively impacted by pathogenic ATN1. RNA-seq identified altered protein quality control and immune pathways in the presence of pathogenic ATN1. Based on these data, we conducted genetic experiments that confirmed the role of protein quality control components that ameliorate or exacerbate ATN1 toxicity. Hsc70-3, a chaperone, arose as a likely suppressor of toxicity. VCP (a proteasome-related AAA ATPase), Rpn11 (a proteasome-related deubiquitinase) and select DnaJ proteins (co-chaperones) were inconsistently protective, depending on the tissues where they were expressed. Lastly, informed by RNA-seq data that exercise-related genes may also be involved in this model of DRPLA, we conducted short-term exercise, which improved overall fly motility. This new model of DRPLA will prove important to understanding this understudied disease and will help to identify therapeutic targets for it.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.