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Use of Proteasome Targeting Small Molecules to Mitigate Muscle Wasting

Small molecules that modulate the activity of the proteasome super-enzyme to alleviate excessive degradation of muscle proteins


Skeletal muscle atrophy and related loss of muscle strength and function originate in disturbed proteostasis: the balance between degradation and synthesis of muscle proteins is tipped toward degradation. The atrophy, or “wasting” is related to significant morbidity and even mortality in chronic diseases such as cancer, AIDS, chronic renal failure, kidney diseases, chronic obstructive pulmonary disease (COPD), multiple sclerosis, cystic fibrosis, rheumatoid arthritis or congestive heart failure. Moreover, muscle wasting and resulting decrease in quality of life follows limb injury, burns and immobilization, and accompanies normal aging. Specific and effective treatments are missing. The essential ubiquitin-proteasome system is responsible for majority of the catabolic processes inside the cell. Consequently, the system and especially its center point protease, the proteasome,

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