ArticleCellular and molecular life sciences : CMLS2010
Downregulation of NF-kappaB signaling by mutant huntingtin proteins induces oxidative stress and cell death.
Article in Cellular and molecular life sciences : CMLS, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Down-regulation of neuroprotective protein kinase D in Huntington´s disease.Cell death & disease · 2025Article
- Transient receptor potential vanilloid 4 blockage attenuates pyroptosis in hippocampus of mice following pilocarpine‑induced status epilepticus.Acta neuropathologica communications · 2025Article
- USP14 is crucial for proteostasis regulation and α-synuclein degradation in human SH-SY5Y dopaminergic cells.Heliyon · 2025Article
- Fueling neurodegeneration: metabolic insights into microglia functions.Journal of neuroinflammation · 2024Review
- Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties.Cell & bioscience · 2023Review
- Molecular Pathophysiological Mechanisms in Huntington's Disease.Biomedicines · 2022Review
- Calpain-mediated proteolysis as driver and modulator of polyglutamine toxicity.Frontiers in molecular neuroscience · 2022Review
- When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer's and Huntington's Disease.International journal of molecular sciences · 2021Review
- Functional analysis of brain derived neurotrophic factor (BDNF) in Huntington's disease.Aging · 2021Article
- Reactive Species in Huntington Disease: Are They Really the Radicals You Want to Catch?Antioxidants (Basel, Switzerland) · 2020Review
- Interaction of Oxidative Stress and Misfolded Proteins in the Mechanism of Neurodegeneration.Life (Basel, Switzerland) · 2020Review
- Quality Control in Huntington's Disease: a Therapeutic Target.Neurotoxicity research · 2019Review
- Dual-Specificity Phosphatase Regulation in Neurons and Glial Cells.International journal of molecular sciences · 2019Review
- Impaired Redox Signaling in Huntington's Disease: Therapeutic Implications.Frontiers in molecular neuroscience · 2019Review
- Heat shock promotes inclusion body formation of mutant huntingtin (mHtt) and alleviates mHtt-induced transcription factor dysfunction.The Journal of biological chemistry · 2018Article
- Transcriptional Dysregulation and Post-translational Modifications in Polyglutamine Diseases: From Pathogenesis to Potential Therapeutic Strategies.Frontiers in molecular neuroscience · 2018Review
- Spinocerebellar Ataxia Type 2 Is Associated with the Extracellular Loss of Superoxide Dismutase but Not Catalase Activity.Frontiers in neurology · 2017Article
- Oxidative Stress and Huntington's Disease: The Good, The Bad, and The Ugly.Journal of Huntington's disease · 2016Review
- Cervical stenosis in spinal cord injury and disorders.The journal of spinal cord medicine · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of abnormal proteins and endoplasmic reticulum stress accompany neurodegenerative diseases including Huntington's disease. We show that the expression of mutant huntingtin proteins with extended polyglutamine repeats differentially affected endoplasmic reticulum signaling cascades linked to the inositol-requiring enzyme-1 (IRE1) pathway. Thus, the p38 and c-Jun N-terminal kinase pathways were activated, while the levels of the nuclear factor-kappaB-p65 (NF-kappaB-p65) protein decreased. Downregulation of NF-kappaB signaling was linked to decreased antioxidant levels, increased oxidative stress, and enhanced cell death. Concomitantly, calpain was activated, and treatment with calpain inhibitors restored NF-kappaB-p65 levels and increased cell viability. The calpain regulator, calpastatin, was low in cells expressing mutant huntingtin, and overexpression of calpastatin counteracted the deleterious effects caused by N-terminal mutant huntingtin proteins. These results show that calpastatin and an altered NF-kappaB-p65 signaling are crucial factors involved in oxidative stress and cell death mediated by mutant huntingtin proteins.
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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.