The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
Age-related Huntington’s disease progression modeled in directly reprogrammed patient-derived striatal neurons highlights impaired autophagy
Open accessAbstract
Huntington's disease (HD) is an inherited neurodegenerative disorder with adult-onset clinical symptoms, but the mechanism by which aging drives the onset of neurodegeneration in patients with HD remains unclear. In this study we examined striatal medium spiny neurons (MSNs) directly reprogrammed from fibroblasts of patients with HD to model the age-dependent onset of pathology. We found that pronounced neuronal death occurred selectively in reprogrammed MSNs from symptomatic patients with HD (HD-MSNs) compared to MSNs derived from younger, pre-symptomatic patients (pre-HD-MSNs) and control MSNs from age-matched healthy individuals. We observed age-associated alterations in chromatin accessibility between HD-MSNs and pre-HD-MSNs and identified miR-29b-3p, whose age-associated upregulation promotes HD-MSN degeneration by impairing autophagic function through human-specific targeting of the STAT3 3' untranslated region. Reducing miR-29b-3p or chemically promoting autophagy increased the resilience of HD-MSNs against neurodegeneration. Our results demonstrate miRNA upregulation with aging in HD as a detrimental process driving MSN degeneration and potential approaches for enhancing autophagy and resilience of HD-MSNs.
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“This miRNA-induced neuronal state can synergize with additional transcription factors (TFs) to generate disease-relevant neuronal subtypes that recapitulate age-dependent neuropathology (26, 28, 30, 31), including primary tauopathy and adult-onset neurodegeneration of Huntington’s disease (20, 32, 33).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [32]
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“Indeed, counteracting aging pathways has been shown to lower age- and disease stage-dependent neurodegeneration in a patient-derived Huntington disease model (32).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [32]
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Tong, H., Yang, T., Xu, S., Li, X., Liu, L., Zhou, G., Yang, S., Yin, S., Li, X., & Li, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073845 · Cited by 142
Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming
Sun, Z., Kwon, J.-S., Ren, Y., Chen, S., Walker, C. K., Lu, X., Cates, K., Karahan, H., Sviben, S., Fitzpatrick, J. A. J., et al. (2024) · Science · doi:10.1126/science.adl2992 · Cited by 77
“…miRNA-induced neuronal state can synergize with additional transcription factors (TFs) to generate disease-relevant neuronal subtypes that recapitulate age-dependent neuropathology (26, 28, 30, 31), including primary tauopathy and adult-onset neurodegeneration of Huntington’s disease (20, 32, 33).”
Self-citationSulfide regulation and catabolism in health and disease
Hou, Y., Lv, B., Du, J., Ye, M., Jin, H., Yi, Y., & Huang, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02231-w · Cited by 56
Metadata
- Authors
- Oh, Y. M., Lee, S. W., Kim, W. K., Chen, S., Church, V. A., Cates, K., Li, T., Zhang, B., Dolle, R. E., Dahiya, S., Pak, S. C., Silverman, G. A., Perlmutter, D. H., & Yoo, A. S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Yoo, Andrew S.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2022-10-27
- Volume
- 25
- Issue
- 11
- Pages
- 1420-1433
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC10162007
- OpenAlex
- W4307498144
- Cited by
- 100
- References
- 60
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 35 · 2023: 22 · 2022: 1
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cellular and Molecular Biology Training Program
- CHDI Foundation
- Cure Alzheimer's Fund
- Hereditary Disease Foundation
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (RF1AG056296)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R01NS107488)
- Farrell Foundation Fund and Mallinckrodt Scholar Award
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Huntington's disease, age-related neurodegeneration, striatal medium spiny neurons, direct reprogramming, fibroblast-to-neuron conversion, autophagy, miR-29b-3p, chromatin accessibility, neuronal cell death, disease onset, patient-derived neurons
- MeSH terms
- Animals, Autophagy, Corpus Striatum, Disease Models, Animal, Humans, Huntington Disease, Neurons, Disease Progression, MicroRNAs
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