The ubiquitin proteasome system and schizophrenia

Lancet Psychiatry. 2020 Jun;7(6):528-537. doi: 10.1016/S2215-0366(19)30520-6. Epub 2020 Feb 12.

Abstract

The ubiquitin-proteasome system is a master regulator of neural development and the maintenance of brain structure and function. It influences neurogenesis, synaptogenesis, and neurotransmission by determining the localisation, interaction, and turnover of scaffolding, presynaptic, and postsynaptic proteins. Moreover, ubiquitin-proteasome system signalling transduces epigenetic changes in neurons independently of protein degradation and, as such, dysfunction of components and substrates of this system has been linked to a broad range of brain conditions. Although links between ubiquitin-proteasome system dysfunction and neurodegenerative disorders have been known for some time, only recently have similar links emerged for neurodevelopmental disorders, such as schizophrenia. Here, we review the components of the ubiquitin-proteasome system that are reported to be dysregulated in schizophrenia, and discuss specific molecular changes to these components that might, in part, explain the complex causes of this mental disorder.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Models, Animal
  • Neurodegenerative Diseases / metabolism
  • Neurodevelopmental Disorders / metabolism
  • Neurogenesis / physiology
  • Neurons / metabolism
  • Presynaptic Terminals / physiology
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Endopeptidase Complex / physiology
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*
  • Schizophrenia / physiopathology
  • Synaptic Transmission / physiology
  • Ubiquitin / metabolism*
  • Ubiquitin / physiology
  • Ubiquitin-Protein Ligases / antagonists & inhibitors*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitin-Protein Ligases / therapeutic use

Substances

  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex