Chemical and Biological Mechanisms Relevant to the Rescue of MG-132-Treated Neurons by Cysteine.

ABSTRACT: Proteasome dysfunctions are observed in many human pathologies. To study their role and potential treatment strategies, models of proteasome inhibition are widely used in biomedical research. One frequently used tool is the proteasome inhibitor MG-132. It triggers the degeneration of human neurons, and several studies show protection from pathological events by glutathione or its precursors. It has therefore been concluded that glutathione protects cells from proteasome dysfunction. However, an alternative explanation is that MG-132, which is a peptide aldehyde, is chemically inactivated by thiols, and the apparent protection by glutathione from proteasome dysfunction is an artefact. To clarify this issue, we examined the chemical inactivation of MG-132 by thiols and the role of such react

SUBMITTER: Uckert AK 

PROVIDER: S-EPMC11851368 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature