Parkin is a disease modifier in the mutant SOD1 mouse model of ALS
| العنوان: | Parkin is a disease modifier in the mutant SOD1 mouse model of ALS |
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| المؤلفون: | Veronica Granatiero, Giovanni Manfredi, Michelle Kang Kim, Gloria M. Palomo, Andrea J. Arreguin, Dazhi Zhao, Hibiki Kawamata, Csaba Konrad, Teresa A. Milner |
| المصدر: | EMBO Molecular Medicine EMBO Molecular Medicine, Vol 10, Iss 10, Pp n/a-n/a (2018) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Medicine (General), amyotrophic lateral sclerosis, animal diseases, Ubiquitin-Protein Ligases, SOD1, MFN2, Mice, Transgenic, Mitochondrion, QH426-470, mitochondria quality control, Parkin, 03 medical and health sciences, R5-920, Superoxide Dismutase-1, Ubiquitin, Mitophagy, Genetics, Animals, Research Articles, biology, Chemistry, Autophagy, nutritional and metabolic diseases, Cell biology, nervous system diseases, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, mitophagy, Mitochondrial biogenesis, Gene Knockdown Techniques, biology.protein, Molecular Medicine, Genetics, Gene Therapy & Genetic Disease, Research Article, Neuroscience |
| الوصف: | Mutant Cu/Zn superoxide dismutase (SOD1) causes mitochondrial alterations that contribute to motor neuron demise in amyotrophic lateral sclerosis (ALS). When mitochondria are damaged, cells activate mitochondria quality control (MQC) mechanisms leading to mitophagy. Here, we show that in the spinal cord of G93A mutant SOD1 transgenic mice (SOD1‐G93A mice), the autophagy receptor p62 is recruited to mitochondria and mitophagy is activated. Furthermore, the mitochondrial ubiquitin ligase Parkin and mitochondrial dynamics proteins, such as Miro1, and Mfn2, which are ubiquitinated by Parkin, and the mitochondrial biogenesis regulator PGC1α are depleted. Unexpectedly, Parkin genetic ablation delays disease progression and prolongs survival in SOD1‐G93A mice, as it slows down motor neuron loss and muscle denervation and attenuates the depletion of mitochondrial dynamics proteins and PGC1α. Our results indicate that Parkin is a disease modifier in ALS, because chronic Parkin‐mediated MQC activation depletes mitochondrial dynamics‐related proteins, inhibits mitochondrial biogenesis, and worsens mitochondrial dysfunction. |
| تدمد: | 1757-4684 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e5cf9305774cecb869dfc72686e2be5 https://pubmed.ncbi.nlm.nih.gov/30126943 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0e5cf9305774cecb869dfc72686e2be5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17574684 |
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