Ubiquitin, Autophagy and Neurodegenerative Diseases

Cells. 2020 Sep 2;9(9):2022. doi: 10.3390/cells9092022.

Abstract

Ubiquitin signals play various roles in proteolytic and non-proteolytic functions. Ubiquitin signals are recognized as targets of the ubiquitin-proteasome system and the autophagy-lysosome pathway. In autophagy, ubiquitin signals are required for selective incorporation of cargoes, such as proteins, organelles, and microbial invaders, into autophagosomes. Autophagy receptors possessing an LC3-binding domain and a ubiquitin binding domain are involved in this process. Autophagy activity can decline as a result of genetic variation, aging, or lifestyle, resulting in the onset of various neurodegenerative diseases. This review summarizes the selective autophagy of neurodegenerative disease-associated protein aggregates via autophagy receptors and discusses its therapeutic application for neurodegenerative diseases.

Keywords: autophagy; autophagy–lysosome pathway; neurodegenerative diseases; ubiquitin; ubiquitin–proteasome system.

Publication types

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

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Aging / pathology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Autophagy / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Lysosomes / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis
  • Sequestosome-1 Protein / genetics
  • Sequestosome-1 Protein / metabolism
  • Signal Transduction
  • Ubiquitin / genetics*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Amyloid beta-Peptides
  • Cell Cycle Proteins
  • Membrane Transport Proteins
  • OPTN protein, human
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Proteasome Endopeptidase Complex