ArticleProceedings of the National Academy of Sciences of the United States of America2022
Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Entorhinal Astrocyte Transplants Restore Spatial Exploration and Alleviate Amyloid-Beta Pathology in Alzheimer's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting the cGAS-STING pathway mitigates Huntington disease pathogenesis in a knock-in mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic Profiling of Huntington's Disease: Insights from CAG Repeat Analysis for Precision Diagnosis and Management.Noro psikiyatri arsivi · 2026Article
- Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- SENP3 protects hepatocyte from pyroptosis during acute liver injury through deSUMOylation of HNRNPL.iScience · 2025Article
- Dysregulation of protein SUMOylation networks in Huntington's disease R6/2 mouse striatum.Brain : a journal of neurology · 2025Article
- Small molecule modulation of p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Ubiquitin specific peptidase 11 knockdown slows Huntington's disease progression via regulating mitochondrial dysfunction and neuronal damage depending on PTEN-mediated AKT pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Protein modification in neurodegenerative diseases.MedComm · 2024Review
- Correction of symptoms of Huntington disease by genistein through FOXO3-mediated autophagy stimulation.Autophagy · 2024Article
- Rhes, a striatal enriched protein, regulates post-translational small-ubiquitin-like-modifier (SUMO) modification of nuclear proteins and alters gene expression.Cellular and molecular life sciences : CMLS · 2024Article
- Retinal dysfunction in Huntington's disease mouse models concurs with local gliosis and microglia activation.Scientific reports · 2024Article
- Curbing Rhes Actions: Mechanism-based Molecular Target for Huntington's Disease and Tauopathies.CNS & neurological disorders drug targets · 2024Review
- The N17 domain of huntingtin as a multifaceted player in Huntington's disease.Frontiers in molecular biosciences · 2024Review
- Paralogue-Specific Roles of SUMO1 and SUMO2/3 in Protein Quality Control and Associated Diseases.Cells · 2023Review
- Article
- Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing.International journal of molecular sciences · 2023Review
- Review
- Review
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
The CAG expansion of huntingtin (mHTT) associated with Huntington disease (HD) is a ubiquitously expressed gene, yet it prominently damages the striatum and cortex, followed by widespread peripheral defects as the disease progresses. However, the underlying mechanisms of neuronal vulnerability are unclear. Previous studies have shown that SUMO1 (small ubiquitin-like modifier-1) modification of mHtt promotes cellular toxicity, but the in vivo role and functions of SUMO1 in HD pathogenesis are unclear. Here, we report that SUMO1 deletion in Q175DN HD-het knockin mice (HD mice) prevented age-dependent HD-like motor and neurological impairments and suppressed the striatal atrophy and inflammatory response. SUMO1 deletion caused a drastic reduction in soluble mHtt levels and nuclear and extracellular mHtt inclusions while increasing cytoplasmic mHtt inclusions in the striatum of HD mice. SUMO1 deletion promoted autophagic activity, characterized by augmented interactions between mHtt inclusions and a lysosomal marker (LAMP1), increased LC3B- and LAMP1 interaction, and decreased interaction of sequestosome-1 (p62) and LAMP1 in DARPP-32-positive medium spiny neurons in HD mice. Depletion of SUMO1 in an HD cell model also diminished the mHtt levels and enhanced autophagy flux. In addition, the SUMOylation inhibitor ginkgolic acid strongly enhanced autophagy and diminished mHTT levels in human HD fibroblasts. These results indicate that SUMO is a critical therapeutic target in HD and that blocking SUMO may ameliorate HD pathogenesis by regulating autophagy activities.
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