ArticleHuman molecular genetics2015
Aged monkey brains reveal the role of ubiquitin-conjugating enzyme UBE2N in the synaptosomal accumulation of mutant huntingtin.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Protein kinase CK2α' as a dual modulator of neuroimmune signaling and synaptic dysfunction in tauopathy.Translational neurodegeneration · 2026Article
- Review
- Inhibition of UBE2N promotes the clearance of mutant HTT (huntingtin) in HD knock-in mice.Autophagy · 2025Article
- Protein kinase CK2α' as a dual modulator of immune signaling and synaptic dysfunction in Tauopathy.bioRxiv : the preprint server for biology · 2025Article
- Identification of UBE2N as a biomarker of Alzheimer's disease by combining WGCNA with machine learning algorithms.Scientific reports · 2025Article
- Quantitative DIA-based proteomics unveils ribosomal biogenesis pathways associated with increased final size in three-year-old Chinese mitten crab (Eriocheir sinensis).BMC genomics · 2025Article
- Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Genetically modified non-human primate models for research on neurodegenerative diseases.Zoological research · 2024Review
- Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis.Journal of periodontal & implant science · 2023Article
- Keeping synapses in shape: degradation pathways in the healthy and aging brain.Neuronal signaling · 2022Review
- Differential Brain and Cerebrospinal Fluid Proteomic Responses to Acute Prenatal Endotoxin Exposure.Molecular neurobiology · 2022Article
- Identification of an miRNA Regulatory Network and Candidate Markers for Ischemic Stroke Related to Diabetes.International journal of general medicine · 2021Article
- Ube2v1 Positively Regulates Protein Aggregation by Modulating Ubiquitin Proteasome System Performance Partially Through K63 Ubiquitination.Circulation research · 2020Article
- UBE2N Regulates Paclitaxel Sensitivity of Ovarian Cancer via Fos/P53 Axis.OncoTargets and therapy · 2020Article
- Deregulation of LRSAM1 expression impairs the levels of TSG101, UBE2N, VPS28, MDM2 and EGFR.PloS one · 2019Article
- The inhibition of UBC13 expression and blockage of the DNMT1-CHFR-Aurora A pathway contribute to paclitaxel resistance in ovarian cancer.Cell death & disease · 2018Article
- Life and death in the trash heap: The ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral Ischemia.Ageing research reviews · 2017Review
- Ubc13: the Lys63 ubiquitin chain building machine.Oncotarget · 2016Review
- Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Transgenic animal models for study of the pathogenesis of Huntington's disease and therapy.Drug design, development and therapy · 2015Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Although misfolded proteins are ubiquitinated and cleared by the proteasome, they can accumulate in synapses in aged neurons to promote synaptic dysfunction in a variety of neurodegenerative diseases, including Huntington's disease (HD), which is caused by polyglutamine expansion in huntingtin. The mechanism behind this aging-related phenomenon is unknown and has been difficult to investigate using animals with short life spans. With brain tissues from longer-lived rhesus monkeys of different ages, we found that aging reduces ubiquitin-proteasomal activity and also increases the level of ubiquitin-conjugating enzyme UBE2N (Ubc13) in synaptosomes. Synaptosomal fractions from aged monkey brain increase in vitro ubiquitinated huntingtin, whereas depletion of UBE2N markedly reduces this increase. Overexpressing UBE2N increases the aggregation of mutant huntingtin, and reducing UBE2N attenuates huntingtin aggregation in cellular and mouse models of HD. Our studies suggest that increased UBE2N plays a critical role in the synaptosomal accumulation of mutant huntingtin with age.
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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.