ArticleScientific reports2020
4-Phenylbutyrate ameliorates apoptotic neural cell death in Down syndrome by reducing protein aggregates.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Impaired Activity-Regulated Proteostasis: A Shared Mechanism in Neurodevelopmental Disorders.Biological psychiatry · 2026Review
- NEFL is associated with inhibition of odontoblastic process in odontohypophosphatasia.Journal of bone and mineral metabolism · 2026Article
- Interplay between DYRK1A dosage and aneuploidy-induced neuropathology in Down syndrome.Communications biology · 2026Article
- 4-Phenylbutyrate Induces Functional Elongation of the Microglial Process Through Activation of Akt.Neurochemical research · 2026Article
- Outer membrane vesicles secreted by avian pathogenic Escherichia coli promote its survival within macrophages and systemic infection by inducing endoplasmic reticulum stress-mediated autophagy flux blockade.Veterinary research · 2026Article
- Chromosome duplication causes premature aging via defects in ribosome quality control.PLoS biology · 2025Article
- Premature aging in aneuploid yeast is caused in part by aneuploidy-induced defects in Ribosome Quality Control.bioRxiv : the preprint server for biology · 2024Article
- RUNX1 Upregulation Causes Mitochondrial Dysfunction via Regulating the PI3K-Akt Pathway in iPSC from Patients with Down Syndrome.Molecules and cells · 2023Article
- Review
- From neurodevelopment to neurodegeneration: utilizing human stem cell models to gain insight into Down syndrome.Frontiers in genetics · 2023Review
- Cell models for Down syndrome-Alzheimer's disease research.Neuronal signaling · 2022Review
- Making neurons, made easy: The use of Neurogenin-2 in neuronal differentiation.Stem cell reports · 2022Review
- Fluc-EGFP reporter mice reveal differential alterations of neuronal proteostasis in aging and disease.The EMBO journal · 2021Article
- Alzheimer's disease alters oligodendrocytic glycolytic and ketolytic gene expression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome.Communications biology · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Individuals with Down syndrome (DS) commonly show unique pathological phenotypes throughout their life span. Besides the specific effects of dosage-sensitive genes on chromosome 21, recent studies have demonstrated that the gain of a chromosome exerts an adverse impact on cell physiology, regardless of the karyotype. Although dysregulated transcription and perturbed protein homeostasis are observed in common in human fibroblasts with trisomy 21, 18, and 13, whether and how this aneuploidy-associated stress acts on other cell lineages and affects the pathophysiology are unknown. Here, we investigated cellular stress responses in human trisomy 21 and 13 neurons differentiated from patient-derived induced pluripotent stem cells. Neurons of both trisomies showed increased vulnerability to apoptotic cell death, accompanied by dysregulated protein homeostasis and upregulation of the endoplasmic reticulum stress pathway. In addition, misfolded protein aggregates, comprising various types of neurodegenerative disease-related proteins, were abnormally accumulated in trisomic neurons. Intriguingly, treatment with sodium 4-phenylbutyrate, a chemical chaperone, successfully decreased the formation of protein aggregates and prevented the progression of cell apoptosis in trisomic neurons. These results suggest that aneuploidy-associated stress might be a therapeutic target for the neurodegenerative phenotypes in DS.
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