دورية أكاديمية
Converging Role for REEP1/SPG31 in Oxidative Stress
| العنوان: | Converging Role for REEP1/SPG31 in Oxidative Stress |
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| المؤلفون: | Valentina Naef, Maria C. Meschini, Alessandra Tessa, Federica Morani, Debora Corsinovi, Asahi Ogi, Maria Marchese, Michela Ori, Filippo M. Santorelli, Stefano Doccini |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 4, p 3527 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | mitochondria, REEP1, SPG31, bioenergetic defects, ROS, zebrafish, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Mutations in the receptor expression-enhancing protein 1 gene (REEP1) are associated with hereditary spastic paraplegia type 31 (SPG31), a neurological disorder characterized by length-dependent degeneration of upper motor neuron axons. Mitochondrial dysfunctions have been observed in patients harboring pathogenic variants in REEP1, suggesting a key role of bioenergetics in disease-related manifestations. Nevertheless, the regulation of mitochondrial function in SPG31 remains unclear. To elucidate the pathophysiology underlying REEP1 deficiency, we analyzed in vitro the impact of two different mutations on mitochondrial metabolism. Together with mitochondrial morphology abnormalities, loss-of-REEP1 expression highlighted a reduced ATP production with increased susceptibility to oxidative stress. Furthermore, to translate these findings from in vitro to preclinical models, we knocked down REEP1 in zebrafish. Zebrafish larvae showed a significant defect in motor axon outgrowth leading to motor impairment, mitochondrial dysfunction, and reactive oxygen species accumulation. Protective antioxidant agents such as resveratrol rescued free radical overproduction and ameliorated the SPG31 phenotype both in vitro and in vivo. Together, our findings offer new opportunities to counteract neurodegeneration in SPG31. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/4/3527; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms24043527 |
| URL الوصول: | https://doaj.org/article/3bf6ef1986dc49d9aebc8eaf92554223 |
| رقم الأكسشن: | edsdoj.3bf6ef1986dc49d9aebc8eaf92554223 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms24043527 |