Inhibited inositol monophosphatase and decreased myo‐inositol concentration improve wasting in skeletal muscles

Lee, Ji-Hyung; Kim, Hyun-Jun; Kim, Seon Wook; Um, JungIn; Jung, Dawoon; Williams, Darren R.

doi:10.1002/ctm2.251

Cited by 2 publications

(3 citation statements)

References 10 publications

(17 reference statements)

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“…Western blotting was carried out using the previously published protocol [67]. The NIH imaging software Image J 64 was used for densitometry analysis of the gel bands.…”

Section: Methodsmentioning

confidence: 99%

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Targeting phosphatase DUSP22 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression

Lee,

Kim,

Kim

et al. 2024

Preprint

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Skeletal muscle wasting results from numerous conditions, such as sarcopenia, glucocorticoid therapy or intensive care. It prevents independent living in the elderly, predisposes to secondary diseases, and ultimately reduces lifespan. There is no approved drug therapy and the major causative mechanisms are not fully understood. Dual specificity phosphatase 22 (DUSP22) is a pleiotropic signaling molecule that plays important roles in immunity and cancer. However, the role of DUSP22 in skeletal muscle wasting is unknown. In this study, DUSP22 was found to be upregulated in sarcopenia patients and models of skeletal muscle wasting. DUSP22 knockdown or pharmacological inhibition prevented multiple forms of muscle wasting. Mechanistically, targeting DUSP22 suppressed FOXO3a, a master regulator of skeletal muscle wasting, via downregulation of the stress-activated kinase JNK, which occurred independently of aberrant Akt activation. DUSP22 targeting was also effective in human skeletal muscle cells undergoing atrophy. In conclusion, phosphatase DUSP22 is a novel target for preventing skeletal muscle wasting. The DUSP22-JNK-FOXO3a axis could be exploited to treat sarcopenia or related aging disorders.

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“…Western blotting was carried out using the previously published protocol [67]. The NIH imaging software Image J 64 was used for densitometry analysis of the gel bands.…”

Section: Methodsmentioning

confidence: 99%

“…An AccuPower RT PreMix (Bioneer, Republic of Korea) was used to synthesize the cDNA from total RNA. The real-time PCR (qPCR) was carried out according to the manufacturer’s instructions, and the previously published protocol [67]. The primers used in this study are shown in reagent and tools table.…”

Section: Methodsmentioning

confidence: 99%

Targeting phosphatase DUSP22 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression

Lee,

Kim,

Kim

et al. 2024

Preprint

Self Cite

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“…Lee at al. investigated the effects of ebselen, an IMPase inhibitor with reduced toxicity, in a glycerol treatment model that models the skeletal muscle fat cell accumulation observed in sarcopenia [170,171]. Ebselen improved muscle performance, as measured by latency to fall in the rotarod test, increased myofiber CSA in the gastrocnemius muscle, and downregulated atrogin-1 and MuRF-1 expression [172].…”

Section: Drug Repositioningmentioning

confidence: 99%

Age Is Just a Number: Progress and Obstacles in the Discovery of New Candidate Drugs for Sarcopenia

Kim,

Jung,

Williams

2023

Cells

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Sarcopenia is a disease characterized by the progressive loss of skeletal muscle mass and function that occurs with aging. The progression of sarcopenia is correlated with the onset of physical disability, the inability to live independently, and increased mortality. Due to global increases in lifespan and demographic aging in developed countries, sarcopenia has become a major socioeconomic burden. Clinical therapies for sarcopenia are based on physical therapy and nutritional support, although these may suffer from low adherence and variable outcomes. There are currently no clinically approved drugs for sarcopenia. Consequently, there is a large amount of pre-clinical research focusing on discovering new candidate drugs and novel targets. In this review, recent progress in this research will be discussed, along with the challenges that may preclude successful translational research in the clinic. The types of drugs examined include mitochondria-targeting compounds, anti-diabetes agents, small molecules that target non-coding RNAs, protein therapeutics, natural products, and repositioning candidates. In light of the large number of drugs and targets being reported, it can be envisioned that clinically approved pharmaceuticals to prevent the progression or even mitigate sarcopenia may be within reach.

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Inhibited inositol monophosphatase and decreased myo‐inositol concentration improve wasting in skeletal muscles

Cited by 2 publications

References 10 publications

Targeting phosphatase DUSP22 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression

Targeting phosphatase DUSP22 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression

Age Is Just a Number: Progress and Obstacles in the Discovery of New Candidate Drugs for Sarcopenia

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