ArticleF1000Research2015
The unfolded protein response and its potential role in Huntington's disease elucidated by a systems biology approach.
Article in F1000Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- The Role of High Mobility Group Box 1 (HMGB1) in Neurodegeneration: A Systematic Review.Current neuropharmacology · 2022Pooled it
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- Cardiomyocyte-derived exosomes carrying miR-181a-5p facilitate heart-brain crosstalk and exacerbate methamphetamine dependence in rats.Frontiers in pharmacology · 2025Article
- The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery.Autophagy reports · 2025Review
- Restoring Compromised ClThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Review
- Multi-omic analysis of Huntington's disease reveals a compensatory astrocyte state.Nature communications · 2024Article
- A network-based transcriptomic landscape of HepG2 cells uncovering causal gene-cytotoxicity interactions underlying drug-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Multi-OMIC analysis of Huntington disease reveals a neuroprotective astrocyte state.bioRxiv : the preprint server for biology · 2023Article
- SIGMAR1 Confers Innate Resilience against Neurodegeneration.International journal of molecular sciences · 2023Review
- miR-34a-5p as molecular hub of pathomechanisms in Huntington's disease.Molecular medicine (Cambridge, Mass.) · 2023Article
- A Novel Huntington's Disease Assessment Platform to Support Future Drug Discovery and Development.International journal of molecular sciences · 2022Article
- Analysis of Huntington's Disease Modifiers Using the Hyperbolic Mapping of the Protein Interaction Network.International journal of molecular sciences · 2022Article
- Downregulation of neurodevelopmental gene expression in iPSC-derived cerebral organoids upon infection by human cytomegalovirus.iScience · 2022Article
- Impaired inhibitory GABAergic synaptic transmission and transcription studied in single neurons by Patch-seq in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Neurodegenerative Disease and the NLRP3 Inflammasome.Frontiers in pharmacology · 2021Review
- Striatal Chloride Dysregulation and Impaired GABAergic Signaling Due to Cation-Chloride Cotransporter Dysfunction in Huntington's Disease.Frontiers in cellular neuroscience · 2021Review
- Dynamic changes in the brain protein interaction network correlates with progression of Aβ42 pathology in Drosophila.Scientific reports · 2020Article
- Sorcin is an early marker of neurodegeneration, CaCell death & disease · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington ´s disease (HD) is a progressive, neurodegenerative disease with a fatal outcome. Although the disease-causing gene (huntingtin) has been known for over 20 years, the exact mechanisms leading to neuronal cell death are still controversial. One potential mechanism contributing to the massive loss of neurons observed in the brain of HD patients could be the unfolded protein response (UPR) activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER). As an adaptive response to counter-balance accumulation of un- or misfolded proteins, the UPR upregulates transcription of chaperones, temporarily attenuates new translation, and activates protein degradation via the proteasome. However, persistent ER stress and an activated UPR can also cause apoptotic cell death. Although different studies have indicated a role for the UPR in HD, the evidence remains inconclusive. Here, we present extensive bioinformatic analyses that revealed UPR activation in different experimental HD models based on transcriptomic data. Accordingly, we have identified 53 genes, including RAB5A, HMGB1, CTNNB1, DNM1, TUBB, TSG101, EEF2, DYNC1H1, SLC12A5, ATG5, AKT1, CASP7 and SYVN1 that provide a potential link between UPR and HD. To further elucidate the potential role of UPR as a disease-relevant process, we examined its connection to apoptosis based on molecular interaction data, and identified a set of 40 genes including ADD1, HSP90B1, IKBKB, IKBKG, RPS3A and LMNB1, which seem to be at the crossroads between these two important cellular processes. Remarkably, we also found strong correlation of UPR gene expression with the length of the polyglutamine tract of Huntingtin, which is a critical determinant of age of disease onset in human HD patients pointing to the UPR as a promising target for therapeutic intervention. The study is complemented by a newly developed web-portal called UPR-HD (http://uprhd.sysbiolab.eu) that enables visualization and interactive analysis of UPR-associated gene expression across various HD models.
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