ArticleThe Journal of clinical investigation2016
Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- ATF6 activation promotes tumorigenesis and drug resistance in diffuse large B-cell lymphoma (DLBCL) by regulating the mTOR/S6K signaling pathway.Discover oncology · 2025Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
- Potential Role of Endoplasmic Reticulum Stress in Modulating Protein Homeostasis in Oligodendrocytes to Improve White Matter Injury in Preterm Infants.Molecular neurobiology · 2024Review
- Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus.Science advances · 2024Article
- Article
- Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer.Molecular medicine (Cambridge, Mass.) · 2024Review
- Review
- Stress and the domestic cat: have humans accidentally created an animal mimic of neurodegeneration?Frontiers in neurology · 2024Review
- Repaglinide Induces ATF6 Processing and Neuroprotection in Transgenic SOD1G93A Mice.International journal of molecular sciences · 2023Article
- The Unfolded Protein Response: A Double-Edged Sword for Brain Health.Antioxidants (Basel, Switzerland) · 2023Review
- KCells · 2023Review
- Blood RNA transcripts reveal similar and differential alterations in fundamental cellular processes in Alzheimer's disease and other neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Emerging Role of DREAM in Healthy Brain and Neurological Diseases.International journal of molecular sciences · 2023Review
- Impact of ER Stress and ER-Mitochondrial Crosstalk in Huntington's Disease.International journal of molecular sciences · 2022Review
- Nucleolar stress controls mutant Huntington toxicity and monitors Huntington's disease progression.Cell death & disease · 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
- MBTPS2, a membrane bound protease, underlying several distinct skin and bone disorders.Journal of translational medicine · 2021Review
- Pharmacological Approaches for the Modulation of the Potassium Channel KInternational journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD.
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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.