ArticleHuman molecular genetics2013
Elevated NADPH oxidase activity contributes to oxidative stress and cell death in Huntington's disease.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 93 citations in OpenAlex.
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- Mitochondria in Huntington's disease: implications in pathogenesis and mitochondrial-targeted therapeutic strategies.Neural regeneration research · 2023Review
- Diapocynin neuroprotective effects in 3-nitropropionic acid Huntington's disease model in rats: emphasis on Sirt1/Nrf2 signaling pathway.Inflammopharmacology · 2022Article
- NADPH Oxidase: a Possible Therapeutic Target for Cognitive Impairment in Experimental Cerebral Malaria.Molecular neurobiology · 2022Article
- Photodynamic treatment modulates various GTPase and cellular signalling pathways in Tauopathy.Small GTPases · 2022Article
- Article
- Stress-Sensitive Protein Rac1 and Its Involvement in Neurodevelopmental Disorders.Neural plasticity · 2020Review
- The role of NOX inhibitors in neurodegenerative diseases.IBRO reports · 2019Review
- Reformulating Pro-Oxidant Microglia in Neurodegeneration.Journal of clinical medicine · 2019Review
- The Mitochondrial Targets of Neuroprotective Drug Vinpocetine on Primary Neuron Cultures, Brain Capillary Endothelial Cells, Synaptosomes, and Brain Mitochondria.Neurochemical research · 2019Article
- Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities.Antioxidants & redox signaling · 2019Review
- Neuroprotective mechanisms of dieckol against glutamate toxicity through reactive oxygen species scavenging and nuclear factor-like 2/heme oxygenase-1 pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Article
- Rac1 Activity Is Modulated by Huntingtin and Dysregulated in Models of Huntington's Disease.Journal of Huntington's disease · 2019Article
- Mitochondrial alterations accompanied by oxidative stress conditions in skin fibroblasts of Huntington's disease patients.Metabolic brain disease · 2018Article
- LncRNAs expression signatures of human brain arteriovenous malformation revealed by microarray.Medicine · 2018Observational
- Neuronal Cell Death.Physiological reviews · 2018Review
- HACE1 is essential for astrocyte mitochondrial function and influences Huntington disease phenotypes in vivo.Human molecular genetics · 2018Article
- A Mitochondria-Associated Oxidative Stress Perspective on Huntington's Disease.Frontiers in molecular neuroscience · 2018Review
- Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models.Cell research · 2017Article
- Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms.Small GTPases · 2017Review
Corrections and comments
- Retraction · 2017-08-22Error in Results and/or Conclusions · Falsification/Fabrication of Data · Falsification/Fabrication of Image · Investigation by Company/Institution · Original Data and/or Images not Provided and/or not Available ·
- Retracted
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
A mutation in the huntingtin (Htt) gene produces mutant Htt and Huntington's disease (HD), a neurodegenerative disorder. HD patients have oxidative damage in the brain, but the causes are unclear. Compared with controls, we found brain levels of NADPH oxidase (NOX) activity, which produces reactive oxygen species (ROS), elevated in human HD postmortem cortex and striatum and highest in striatum of presymptomatic individuals. Synaptosome fractions from cortex and striatum of HD(140Q/140Q) mice had elevated NOX activity at 3 months of age and a further rise at 6 and 12 months compared with synaptosomes of age-matched wild-type (WT) mice. High NOX activity in primary cortical and striatal neurons of HD(140Q/140Q) mice correlated with more ROS and neurite swellings. These features and neuronal cell death were markedly reduced by treatment with NOX inhibitors such as diphenyleneiodonium (DPI), apocynin (APO) and VAS2870. The rise in ROS levels in mitochondria of HD(140Q/140Q) neurons followed the rise in NOX activity and inhibiting only mitochondrial ROS was not neuroprotective. Mutant Htt colocalized at plasma membrane lipid rafts with gp91-phox, a catalytic subunit for the NOX2 isoform. Assembly of NOX2 components at lipid rafts requires activation of Rac1 which was also elevated in HD(140Q/140Q) neurons. HD(140Q/140Q) mice bred to gp91-phox knock-out mice had lower NOX activity in the brain and in primary neurons, and neurons had normal ROS levels and significantly improved survival. These findings suggest that increased NOX2 activity at lipid rafts is an early and major source of oxidative stress and cell death in HD(140Q/140Q) neurons.
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Registered trials
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