Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease
| العنوان: | Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease |
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| المؤلفون: | Michael P. Murphy, Charles Joseph O'Kane, Phoebe Heard, Angeleen Fleming, Claudia Rose, David C. Rubinsztein, Sovan Sarkar, Gauri Krishna, Marie Quick, Moisés García-Arencibia, Benjamin R. Underwood, Viktor I. Korolchuk, Maurizio Renna, Sara Imarisio |
| المساهمون: | Underwood, Benjamin [0000-0003-3427-9487], Fleming, Angeleen [0000-0003-3721-7126], O'Kane, Cahir [0000-0002-3488-2078], Murphy, Mike [0000-0003-1115-9618], Rubinsztein, David [0000-0001-5002-5263], Apollo - University of Cambridge Repository, Underwood, Benjamin R., Imarisio, Sara, Fleming, Angeleen, Rose, Claudia, Krishna, Gauri, Heard, Phoebe, Quick, Marie, Korolchuk, Viktor I., Renna, Maurizio, Sarkar, Sovan, García-arencibia, Moisé, O'Kane, Cahir J., Murphy, Michael P., Rubinsztein, David C. |
| المصدر: | Human Molecular Genetics |
| بيانات النشر: | Oxford University Press (OUP), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Antioxidant, medicine.medical_treatment, Cercopithecus aethiop, Disease, HeLa Cell, medicine.disease_cause, Antioxidants, Mice, 0302 clinical medicine, Chlorocebus aethiops, Zebrafish, Genetics (clinical), chemistry.chemical_classification, 0303 health sciences, Neurodegeneration, Neurodegenerative Diseases, Articles, General Medicine, 3. Good health, Cell biology, Biochemistry, Peptide, COS Cells, Toxicity, Drosophila, Reactive Oxygen Specie, Human, Biology, 03 medical and health sciences, Genetic, COS Cell, Autophagy, Genetics, medicine, Animals, Humans, Molecular Biology, 030304 developmental biology, Reactive oxygen species, Neurodegenerative Disease, Animal, Oxidative Stre, medicine.disease, biology.organism_classification, Mice, Inbred C57BL, Disease Models, Animal, Oxidative Stress, chemistry, Peptides, Reactive Oxygen Species, 030217 neurology & neurosurgery, Oxidative stress, HeLa Cells |
| الوصف: | Many neurodegenerative diseases exhibit protein accumulation and increased oxidative stress. Therapeutic strategies include clearing aggregate-prone proteins by enhancing autophagy or decreasing oxidative stress with antioxidants. Many autophagy-inducing stimuli increase reactive oxygen species (ROS), raising concerns that the benefits of autophagy up-regulation may be counterbalanced by ROS toxicity. Here we show that not all autophagy inducers significantly increase ROS. However, many antioxidants inhibit both basal and induced autophagy. By blocking autophagy, antioxidant drugs can increase the levels of aggregate-prone proteins associated with neurodegenerative disease. In fly and zebrafish models of Huntington's disease, antioxidants exacerbate the disease phenotype and abrogate the rescue seen with autophagy-inducing agents. Thus, the potential benefits in neurodegenerative diseases of some classes of antioxidants may be compromised by their autophagy-blocking properties. |
| وصف الملف: | application/pdf |
| تدمد: | 1460-2083 0964-6906 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0840f5420c83edef34f71184b374039Test https://doi.org/10.1093/hmg/ddq253Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b0840f5420c83edef34f71184b374039 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602083 09646906 |
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