Methods for the discovery of small molecules to monitor and perturb the activity of the human proteasome.

Autor: Maresh ME; Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, 575 West Stadium Avenue, West Lafayette, IN 47907, USA., Salazar-Chaparro AF; Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, 575 West Stadium Avenue, West Lafayette, IN 47907, USA., Trader DJ; Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, 575 West Stadium Avenue, West Lafayette, IN 47907, USA.
Jazyk: angličtina
Zdroj: Future medicinal chemistry [Future Med Chem] 2021 Jan; Vol. 13 (2), pp. 99-116. Date of Electronic Publication: 2020 Dec 04.
DOI: 10.4155/fmc-2020-0288
Abstrakt: 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.
Databáze: MEDLINE