ArticleHuman molecular genetics2018
HACE1 is essential for astrocyte mitochondrial function and influences Huntington disease phenotypes in vivo.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.Molecular and cellular biochemistry · 2026Review
- Intersection of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Neuroinflammation in Huntington's disease: Causes, consequences, and treatment strategies.Journal of Huntington's disease · 2025Review
- Mitochondria from huntington´s disease striatal astrocytes are hypermetabolic and compromise neuronal branching.Cell communication and signaling : CCS · 2025Article
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- Protein modification in neurodegenerative diseases.MedComm · 2024Review
- Unveiling the role of HACE1 in cervical cancer: implications for human papillomavirus infection and prognosis.Translational cancer research · 2024Article
- A Missense Variant inGenes · 2024Article
- Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1.Nature structural & molecular biology · 2024Article
- Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation.Journal of Cancer · 2024Article
- The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection.CNS & neurological disorders drug targets · 2024Review
- Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells.Journal of translational medicine · 2023Review
- Ubiquitin-modifying enzymes in Huntington's disease.Frontiers in molecular biosciences · 2023Review
- Antisense Oligonucleotide Therapy: From Design to the Huntington Disease Clinic.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- Neuroinflammation in Huntington's Disease: A Starring Role for Astrocyte and Microglia.Current neuropharmacology · 2022Review
- Inborn errors of metabolism associated with 3-methylglutaconic aciduria.Clinica chimica acta; international journal of clinical chemistry · 2021Review
- Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders.International journal of molecular sciences · 2021Review
- Review
- The Sigma-1 Receptor Mediates Pridopidine Rescue of Mitochondrial Function in Huntington Disease Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Oxidative stress is a prominent feature of Huntington disease (HD), and we have shown previously that reduced levels of hace1 (HECT domain and Ankyrin repeat containing E3 ubiquitin protein ligase 1) in patient striatum may contribute to the pathogenesis of HD. Hace1 promotes the stability of Nrf2 and thus plays an important role in antioxidant response mechanisms, which are dysfunctional in HD. Moreover, hace1 overexpression mitigates mutant huntingtin (mHTT)-induced oxidative stress in vitro through promotion of the Nrf2 antioxidant response. Here, we show that the genetic ablation of hace1 in the YAC128 mouse model of HD accelerates motor deficits and exacerbates cognitive and psychiatric phenotypes in vivo. We find that both the expression of mHTT and the ablation of hace1 alone are sufficient to cause deficits in astrocytic mitochondrial respiration. We confirm the crucial role of hace1 in astrocytes in vivo, since its ablation is sufficient to cause dramatic astrogliosis in wild-type FVB/N mice. Astrogliosis is not observed in the presence of mHTT but a strong dysregulation in the expression of astrocytic markers in HACE1-/- x YAC128 striatum suggests an additive effect of mHTT expression and hace1 loss on this cell type. HACE1-/- x YAC128 mice and primary cells derived from these animals therefore provide model systems that will allow for the further dissection of Nrf2 pathways and astrocyte dysfunction in the context of HD.
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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 OpenQuestion graph.