ArticleThe Journal of biological chemistry2012
Dithiol-based compounds maintain expression of antioxidant protein peroxiredoxin 1 that counteracts toxicity of mutant huntingtin.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Peroxiredoxin 1 inhibits streptozotocin-induced Alzheimer's disease-like pathology in hippocampal neuronal cells via the blocking of CaScientific reports · 2024Article
- The Role of the Thioredoxin System in Brain Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress.Frontiers in pharmacology · 2022Review
- Social modulation of ageing: mechanisms, ecology, evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2021Review
- Human Huntington's disease pluripotent stem cell-derived microglia develop normally but are abnormally hyper-reactive and release elevated levels of reactive oxygen species.Journal of neuroinflammation · 2021Article
- Peroxiredoxins in Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Mild Exercise Differently Affects Proteostasis and Oxidative Stress on Motor Areas During Neurodegeneration: A Comparative Study of Three Treadmill Running Protocols.Neurotoxicity research · 2019Article
- Neuronal Cells Rearrangement During Aging and Neurodegenerative Disease: Metabolism, Oxidative Stress and Organelles Dynamic.Frontiers in molecular neuroscience · 2019Article
- Review
- Role of Peroxiredoxin 2 in the Protection Against Ferrous Sulfate-Induced Oxidative and Inflammatory Injury in PC12 Cells.Cellular and molecular neurobiology · 2018Article
- A Mitochondria-Associated Oxidative Stress Perspective on Huntington's Disease.Frontiers in molecular neuroscience · 2018Review
- Oxidative Stress and the Central Nervous System.The Journal of pharmacology and experimental therapeutics · 2017Review
- Oxidative Stress and Huntington's Disease: The Good, The Bad, and The Ugly.Journal of Huntington's disease · 2016Review
- Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls.Aging cell · 2016Article
- The Association of VDAC with Cell Viability of PC12 Model of Huntington's Disease.Frontiers in oncology · 2016Article
- Thiol-disulfide Oxidoreductases TRX1 and TMX3 Decrease Neuronal Atrophy in a Lentiviral Mouse Model of Huntington's Disease.PLoS currents · 2015Article
- Nitrosative stress induces peroxiredoxin 1 ubiquitination during ischemic insult via E6AP activation in endothelial cells both in vitro and in vivo.Antioxidants & redox signaling · 2014Article
- Article
- Oxidative stress and neurodegenerative disorders.International journal of molecular sciences · 2013Review
- Role of oxidative DNA damage in mitochondrial dysfunction and Huntington's disease pathogenesis.Free radical biology & medicine · 2013Review
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
Mitochondrial dysfunction and elevated reactive oxygen species are strongly implicated in both aging and various neurodegenerative disorders, including Huntington disease (HD). Because reactive oxygen species can promote the selective oxidation of protein cysteine sulfhydryl groups to disulfide bonds we examined the spectrum of disulfide-bonded proteins that were specifically altered in a HD context. Protein extracts from PC12 cells overexpressing the amino-terminal fragment of the Huntingtin (Htt) protein with either a nonpathogenic or pathogenic polyglutamine repeat (Htt-103Q) were resolved by redox two-dimensional PAGE followed by mass spectrometry analysis. Several antioxidant proteins were identified that exhibited changes in disulfide bonding unique to Htt-103Q expressing cells. In particular, the antioxidant protein peroxiredoxin 1 (Prx1) exhibited both decreased expression and hyperoxidation in response to mutant Htt expressed in either PC12 cells or immortalized striatal cells exposed to 3-nitropropionic acid. Ectopic expression of Prx1 in PC12 cells attenuated mutant Htt-induced toxicity. In contrast, short hairpin RNA-mediated knockdown of Prx1 potentiated mHtt toxicity. Furthermore, treatment with the dithiol-based compounds dimercaptopropanol and dimercaptosuccinic acid suppressed toxicity in both HD cell models, whereas monothiol compounds were relatively ineffective. Dimercaptopropanol treatment also prevented mutant Htt-induced loss of Prx1 expression in both cell models. Our studies reveal for the first time that pathogenic Htt can affect the expression and redox state of antioxidant proteins; an event countered by specific dithiol-based compounds. These findings should provide a catalyst to explore the use of dithiol-based drugs for the treatment of neurodegenerative diseases.
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