ArticleInternational journal of molecular sciences2019
Juvenile Huntington's Disease Skin Fibroblasts Respond with Elevated Parkin Level and Increased Proteasome Activity as a Potential Mechanism to Counterbalance the Pathological Consequences of Mutant Huntingtin Protein.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Dysregulation of store-operated calcium entry in fibroblast lines from adult and juvenile-onset Huntington's disease patients.Pharmacological reports : PR · 2026Article
- Huntingtin in the amygdaloid basolateral complex is correlated with Vonsattel staging in Huntington's disease.Brain communications · 2026Article
- From Skin to Brain: Key Genetic Mediators Associating Cutaneous Inflammation and Neurodegenerative Diseases.Genes · 2025Review
- Exploring the skin as an open window onto neurodegenerative diseases.Translational neurodegeneration · 2025Review
- An emerging role of mitochondrial quality control in bone metabolism: from molecular mechanisms to targeted therapeutic interventions.Cellular and molecular life sciences : CMLS · 2025Review
- Review
- Mitochondria in Huntington's disease: implications in pathogenesis and mitochondrial-targeted therapeutic strategies.Neural regeneration research · 2023Review
- The Potential of Edible and Medicinal Resource Polysaccharides for Prevention and Treatment of Neurodegenerative Diseases.Biomolecules · 2023Review
- Ubiquitin-modifying enzymes in Huntington's disease.Frontiers in molecular biosciences · 2023Review
- Article
- Macroautophagy and Mitophagy in Neurodegenerative Disorders: Focus on Therapeutic Interventions.Biomedicines · 2021Review
- The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin.Biomolecules · 2020Article
- How Do Post-Translational Modifications Influence the Pathomechanistic Landscape of Huntington's Disease? A Comprehensive Review.International journal of molecular sciences · 2020Review
- The proteasome activator PA200 regulates expression of genes involved in cell survival upon selective mitochondrial inhibition in neuroblastoma cells.Journal of cellular and molecular medicine · 2020Article
- Targeting Nuclear NADCancers · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Huntington's disease (HD) is an inherited neurodegenerative disorder, caused by an abnormal polyglutamine (polyQ) expansion in the huntingtin protein (Htt). Mitochondrial dysfunction and impairment of the ubiquitin-proteasome system (UPS) are hallmarks of HD neurons. The extraneural manifestations of HD are still unclear. We investigated the crosstalk between mitochondria and proteolytic function in skin fibroblasts from juvenile HD patients. We found reduced mitosis, increased cell size, elevated ROS and increased mitochondrial membrane potential in juvenile HD fibroblasts, while cellular viability was maintained. Mitochondrial OXPHOS analysis did not reveal significant differences compared to control. However, the level of mitochondrial fusion and fission proteins was significantly lower and branching in the mitochondria network was reduced. We hypothesized that juvenile HD fibroblasts counterbalance cellular damage and mitochondrial network deficit with altered proteasome activity to promote cell survival. Our data reveal that juvenile HD fibroblasts exhibit higher proteasome activity, which was associated with elevated gene and protein expression of parkin. Moreover, we demonstrate elevated proteasomal degradation of the mitochondrial fusion protein Mfn1 in diseased cells compared to control cells. Our data suggest that juvenile HD fibroblasts respond to mutant polyQ expansion of Htt with enhanced proteasome activity and faster turnover of specific UPS substrates to protect cells.
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