The proteasome and its role in the nervous system

Cell Chem Biol. 2021 Jul 15;28(7):903-917. doi: 10.1016/j.chembiol.2021.04.003. Epub 2021 Apr 26.


Proteasomes are multisubunit complexes that catalyze the majority of protein degradation in mammalian cells to maintain protein homeostasis and influence the regulation of most cellular processes. The proteasome, a multicatalytic protease complex, is a ring-like structure with a narrow pore that exhibits regulated gating, enabling the selective degradation of target proteins into peptide fragments. This process of removing proteins is essential for eliminating proteins that are no longer wanted, such as unfolded or aggregated proteins. This is important for preserving cellular function relevant to brain health and disease. Recently, in the nervous system, specialized proteasomes have been shown to generate peptides with important cellular functions. These discoveries challenge the prevailing notion that proteasomes primarily operate to eliminate proteins and identify signaling-competent proteasomes. This review focuses on the structure, function, and regulation of proteasomes and sheds light on emerging areas of investigation regarding the role of proteasomes in the nervous system.

Keywords: neurodegeneration; neuronal activity; proteasome; ubiquitin-proteasome system.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Nervous System / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*


  • Proteasome Endopeptidase Complex