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Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice

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Sharma, Mridula
Kambadur, Ravi

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Parkinson's Disease (PD) is a chronic and progressive neurodegenerative disease manifesting itself with tremors, muscle stiffness, bradykinesia, dementia, and depression. Mutations of mitochondria! E3 ligase, PARKIN, have been associated with juvenile PD. Previous studies have characterized muscle atrophy and motor deficits upon loss of functional Parkin in fly and rodent models. However, the mechanisms behind pathophysiology of Parkin deficient muscle remains to be elusive. Here, results suggested that knock down of Parkin significantly increases proteolytic activities in skeletal muscle cell line, the C2C12 myotubes. However, the atrogene levels increase moderately in Parkin deficient cell line. To further investigate the role of Parkin in skeletal muscle atrophy, Parkin knock out (KO) and wild type mice were subjected to 48 h starvation. After 48 h fasting, a greater reduction in skeletal muscle weights was observed in Parkin KO mice as compared to age matched wild type control, suggesting elevated proteolytic activity in the absence of Parkin. Subsequent microarray analyses revealed further enhanced expression of FOXO and ubiquitin pathway in fasted Parkin KO mice. Furthermore, a greater reduction in the expression of cytoskeleton genes was observed in Parkin KO mice following 48 h fasting. Collectively, these results suggest that Parkin deficiency exacerbates fasting-induced skeletal muscle wasting, through upregulating genes involved in catabolic activities in skeletal muscle.

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Nature Portfolio

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Neurosciences, Neurology

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NPJ Parkinson's Disease

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10.1038/s41531-022-00419-3

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