Patients with Gaucher disease display systemic oxidative stress dependent on therapy status
| العنوان: | Patients with Gaucher disease display systemic oxidative stress dependent on therapy status |
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| المؤلفون: | Reena V. Kartha, Kyle Rudser, Jeanine Jarnes, Neal J. Weinreb, Roland Brown, Marcia R. Terluk, Usha Mishra, James C. Cloyd, Abigail Travis, Heather Lau |
| المصدر: | Molecular Genetics and Metabolism Reports Molecular Genetics and Metabolism Reports, Vol 25, Iss, Pp 100667-(2020) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | NYU, New York University, Disease, Gaucher disease, medicine.disease_cause, Antioxidants, Lipid peroxidation, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, ACE, angiotensin converting enzyme, TAC, total antioxidant capacity, GSH, glutathione, LC-MS/MS, liquid chromatography-tandem mass spectrometry, TBARS, thiobarbituric acid reactive substances, GD2, Type 2 Gaucher disease, lcsh:QH301-705.5, lcsh:R5-920, 0303 health sciences, GPx, glutathione peroxidase, Parkinsonism, SRT, substrate reduction therapy, 030305 genetics & heredity, Metabolic disorder, GD1, Type 1 Gaucher disease, GD, Gaucher disease, RBC, red blood cell, UMN, University of Minnesota, Glutathione, Pathophysiology, ERT, enzyme replacement therapy, HPLC, high performance liquid chromatography, TRAP, tartrate resistant acid phosphatase, lcsh:Medicine (General), GPG, Glycine-Proline-Glutamate, Research Paper, GSSG, inactive, oxidized form of glutathione, medicine.medical_specialty, CHITO, chitotriosidase, CNS, central nervous system, 03 medical and health sciences, ROS, reactive oxygen species, GCase, glucocerebrosidase, Internal medicine, SOD, superoxide dismutase, Genetics, medicine, Molecular Biology, MDA, malondialdehyde, business.industry, Endoplasmic reticulum, medicine.disease, lcsh:Biology (General), chemistry, Oxidative stress, Lyso-GL1, glucosylsphingosine, Unfolded protein response, business, GD3, Type 3 Gaucher disease, 030217 neurology & neurosurgery |
| الوصف: | Gaucher disease is an autosomal recessive metabolic disorder caused by mutations in GBA1, which encodes for the lysosomal hydrolase enzyme, β-glucocerebrosidase. The resulting misfolded protein can trigger endoplasmic reticulum stress and an unfolded protein response within the affected cells. The enzyme deficiency leads to accumulation of its substrates, glucosylceramide and glucosylsphingosine, within macrophage lysosomes and with prominent disease manifestations in macrophage rich tissues. Resultant lysosomal pathology and impaired autophagy leads to redox imbalance, mitochondrial dysfunction and intracellular oxidative stress. Here we have systematically examined a role for oxidative stress in individuals affected by Gaucher disease. We compared multiple oxidative stress biomarkers in plasma and red blood cell samples from patients who are currently untreated, with those who are stable on standard-of-care therapy, and with healthy controls. We found significant differences in key oxidative stress biomarkers in untreated patients compared to healthy control. In treated patients, results generally fell between the controls and the untreated patients. Interestingly, even asymptomatic and minimally symptomatic untreated patients had evidence of significant systemic oxidative stress. We conclude that underlying oxidative stress may contribute to Gaucher disease pathophysiology including long-term adverse outcomes such as Parkinsonism and malignancies. Therapies targeting oxidative stress may prove useful as adjuvant treatments for Gaucher disease and other lysosomal storage disorders. |
| اللغة: | English |
| تدمد: | 2214-4269 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e464387def65fd2c57de493b1cb23aafTest http://europepmc.org/articles/PMC7733024Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e464387def65fd2c57de493b1cb23aaf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22144269 |
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