Journal
FUTURE MEDICINAL CHEMISTRY
Volume 13, Issue 2, Pages 99-116Publisher
Newlands Press Ltd
DOI: 10.4155/fmc-2020-0288
Keywords
degradation; proteasome; screening
Categories
Funding
- Purdue University Center for Cancer Research NIH [P30 CA023168]
- American Cancer Society Institutional Research Grant [IRG-14-190-56]
- NIH-NIGMS [R21GM131206]
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Regulating protein production and degradation is crucial for cellular homeostasis, with the proteasome playing a key role in maintaining proper protein levels. Disease states such as cancer and neurodegenerative diseases can impact proteasome activity, making it a potential target for therapeutic intervention. Studies involving chemical modulators and inhibitors have shed light on the proteasome's therapeutic potential.
Regulating protein production and degradation is critical to maintaining cellular homeostasis. The proteasome is a key player in keeping proteins at the proper levels. However, proteasome activity can be altered in certain disease states, such as blood cancers and neurodegenerative diseases. Cancers often exhibit enhanced proteasomal activity, as protein synthesis is increased in these cells compared with normal cells. Conversely, neurodegenerative diseases are characterized by protein accumulation, leading to reduced proteasome activity. As a result, the proteasome has emerged as a target for therapeutic intervention. The potential of the proteasome as a therapeutic target has come from studies involving chemical stimulators and inhibitors, and the development of a suite of assays and probes that can be used to monitor proteasome activity with purified enzyme and in live cells.
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