ArticleGenes & development2008
Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.
What it found
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Who cites it
175 citing papers in PubMed, 299 citations in OpenAlex.
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Heavy metal toxicity as a driver of endoplasmic reticulum stress and dysfunction.The FEBS journal · 2026Review
- Disease modeling of myocilin mutation-dependent normal tension glaucoma: human retinal ganglion cell susceptibility to unfolded protein response and mTOR signaling.Stem cells (Dayton, Ohio) · 2026Article
- Advances in Research on Endoplasmic Reticulum-Associated Degradation Mechanisms in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2026Review
- Review
- Generating a Cell Model to Study ER Stress in iPSC-Derived Medium Spiny Neurons from a Patient with Huntington's Disease.International journal of molecular sciences · 2025Article
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.PLoS genetics · 2025Article
- The kinesin Kar3 is required for endoplasmic reticulum-associated degradation.Molecular biology of the cell · 2025Article
- Light-Controlled Intracellular Synthesis of Poly(luciferin) Polymers Induces Cell Paraptosis.Journal of the American Chemical Society · 2025Article
- Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.ACS pharmacology & translational science · 2025Review
- Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington's disease.Nature cell biology · 2024Article
- Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024Review
- UBXN1 maintains ER proteostasis and represses UPR activation by modulating translation.EMBO reports · 2024Article
- Disruption of the nascent polypeptide-associated complex leads to reduced polyglutamine aggregation and toxicity.PloS one · 2024Article
- TOLLIP acts as a cargo adaptor to promote lysosomal degradation of aberrant ER membrane proteins.The EMBO journal · 2023Article
- Proteotoxic stresses stimulate dissociation of UBL4A from the tail-anchored protein recognition complex.The Biochemical journal · 2023Article
- Saccharomyces cerevisiae as a research tool for RNA-mediated human disease.Wiley interdisciplinary reviews. RNA · 2023Review
- From Pathogenesis to Therapeutics: A Review of 150 Years of Huntington's Disease Research.International journal of molecular sciences · 2023Review
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
115 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Protein misfolding, whether caused by aging, environmental factors, or genetic mutations, is a common basis for neurodegenerative diseases. The misfolding of proteins with abnormally long polyglutamine (polyQ) expansions causes several neurodegenerative disorders, such as Huntington's disease (HD). Although many cellular pathways have been documented to be impaired in HD, the primary triggers of polyQ toxicity remain elusive. We report that yeast cells and neuron-like PC12 cells expressing polyQ-expanded huntingtin (htt) fragments display a surprisingly specific, immediate, and drastic defect in endoplasmic reticulum (ER)-associated degradation (ERAD). We further decipher the mechanistic basis for this defect in ERAD: the entrapment of the essential ERAD proteins Npl4, Ufd1, and p97 by polyQ-expanded htt fragments. In both yeast and mammalian neuron-like cells, overexpression of Npl4 and Ufd1 ameliorates polyQ toxicity. Our results establish that impaired ER protein homeostasis is a broad and highly conserved contributor to polyQ toxicity in yeast, in PC12 cells, and, importantly, in striatal cells expressing full-length polyQ-expanded huntingtin.
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Registered trials
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.