ArticleHuman molecular genetics2017
FOXOs modulate proteasome activity in human-induced pluripotent stem cells of Huntington's disease and their derived neural cells.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- The Nematicide Tioxazafen Disrupts Proteasome Function via Cytochrome P450 Bioactivation.bioRxiv : the preprint server for biology · 2026Article
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- Insights into neurodevelopmental features of Huntington's disease from stem cell-derived models including organoids.Journal of Huntington's disease · 2026Review
- Blocking FOXO4 confers neuroprotection against oxidative stress and ischemia-reperfusion caused neuronal injury.Journal of neuropathology and experimental neurology · 2026Article
- Genetic Deletion of Cyclophilin D Results in Enhanced Hypoxia Tolerance in Mice.Cellular and molecular neurobiology · 2026Article
- Proteasomal activity and disease outcome in phenylketonuria patients with a structural SLC7A5 variant.Scientific reports · 2025Article
- Proteasomal dysfunction in the mouse forebrain induces mitochondrial DNA release, cGAS-STING signaling activation, and necroptosis.Journal of neuropathology and experimental neurology · 2025Article
- FOXOs and their roles in acute and chronic neurological disorders.Frontiers in molecular biosciences · 2025Review
- Olfactory Ecto-Mesenchymal Stem Cells in Modeling and Treating Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Therapeutic role of neural stem cells in neurological diseases.Frontiers in bioengineering and biotechnology · 2024Review
- Regulation of mitochondrial function by FOXOs in ischemic stroke and Alzheimer's disease.Organelle (Tucson, Ariz.) · 2024Article
- Structure, Function, and Allosteric Regulation of the 20S Proteasome by the 11S/PA28 Family of Proteasome Activators.Biomolecules · 2023Review
- Role of NFE2L1 in the Regulation of Proteostasis: Implications for Aging and Neurodegenerative Diseases.Biology · 2023Review
- CRISPR/Cas9 Mediated Therapeutic Approach in Huntington's Disease.Molecular neurobiology · 2023Review
- Mesenchymal and Neural Stem Cell-Derived Exosomes in Treating Alzheimer's Disease.Bioengineering (Basel, Switzerland) · 2023Review
- Huntington's disease iPSC models-using human patient cells to understand the pathology caused by expanded CAG repeats.Faculty reviews · 2022Review
- Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation.Biomolecules · 2021Review
- Review
- Patient-derived iPSC modeling of rare neurodevelopmental disorders: Molecular pathophysiology and prospective therapies.Neuroscience and biobehavioral reviews · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Although it has been speculated that proteasome dysfunction may contribute to the pathogenesis of Huntington's disease (HD), a devastating neurodegenerative disorder, how proteasome activity is regulated in HD affected stem cells and somatic cells remains largely unclear. To better understand the pathogenesis of HD, we analyzed proteasome activity and the expression of FOXO transcription factors in three wild-type (WT) and three HD induced-pluripotent stem cell (iPSC) lines. HD iPSCs exhibited elevated proteasome activity and higher levels of FOXO1 and FOXO4 proteins. Knockdown of FOXO4 but not FOXO1 expression decreased proteasome activity. Following neural differentiation, the HD-iPSC-derived neural progenitor cells (NPCs) demonstrated lower levels of proteasome activity and FOXO expressions than their WT counterparts. More importantly, overexpression of FOXO4 but not FOXO1 in HD NPCs dramatically enhanced proteasome activity. When HD NPCs were further differentiated into DARPP32-positive neurons, these HD neurons were more susceptible to death than WT neurons and formed Htt aggregates under the condition of oxidative stress. Similar to HD NPCs, HD-iPSC-derived neurons showed reduced proteasome activity and diminished FOXO4 expression compared to WT-iPSC-derived neurons. Furthermore, HD iPSCs had lower AKT activities than WT iPSCs, whereas the neurons derived from HD iPSC had higher AKT activities than their WT counterparts. Inhibiting AKT activity increased both FOXO4 level and proteasome activity, indicating a potential role of AKT in regulating FOXO levels. These data suggest that FOXOs modulate proteasome activity, and thus represents a potentially valuable therapeutic target for HD.
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