Cellular and Molecular Life Sciences

, Volume 69, Issue 16, pp 2691–2715 | Cite as

Role of the ubiquitin–proteasome system in nervous system function and disease: using C. elegans as a dissecting tool

  • Márcio S. Baptista
  • Carlos B. Duarte
  • Patrícia Maciel


In addition to its central roles in protein quality control, regulation of cell cycle, intracellular signaling, DNA damage response and transcription regulation, the ubiquitin–proteasome system (UPS) plays specific roles in the nervous system, where it contributes to precise connectivity through development, and later assures functionality by regulating a wide spectrum of neuron-specific cellular processes. Aberrations in this system have been implicated in the etiology of neurodevelopmental and neurodegenerative diseases. In this review, we provide an updated view on the UPS and highlight recent findings concerning its role in normal and diseased nervous systems. We discuss the advantages of the model organism Caenorhabditis elegans as a tool to unravel the major unsolved questions concerning this biochemical pathway and its involvement in nervous system function and dysfunction, and expose the new possibilities, using state-of-the-art techniques, to assess UPS function using this model system.


Ubiquitylation E1 E2 E3 De-ubiquitylase Nematode Neurodevelopment Neurodegeneration Synaptic plasticity Neurological disease 







Alzheimer’s disease


Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor


Associated molecule with the SH3 domain of STAM


Anaphase-promoting complex


Activity-regulated cytoskeleton-associated protein


Autism spectrum disorders




Chromatin licensing and DNA replication factor 1


C terminus of Hsc70-interacting protein


Citron kinase


Citron N




Dual-leucine zipper Kinase MAPKKK


Down syndrome


Deubiquitylating enzyme


Deubiquitylating enzymes


Ubiquitin-activating enzyme


Ubiquitin-conjugating enzyme


Ubiquitin ligases


Endoplasmatic reticulum-associated degradation


Gamma-aminobutyric acid


Herpesvirus-associated ubiquitin-specific protease


Huntington’s disease


Hermaphrodite-specific motor neuron




Jab1/MPN domain-associated metalloisopeptidase class


L-α-lysophosphatidic acid


Long-term facilitation


Miniature excitatory postsynaptic currents


Machado–Joseph disease


Nerve growth factor


Otubain protease


Protein associated with myc


Parkinson’s disease


Peptidyl-glutamyl peptide-hydrolyzing


Protein kinase A




Primary synapse region


Regulator of pre-synaptic morphology-1


Repressor element 1-silencing transcription factor


Rab3-interacting molecule 1


Spinocerebellar ataxia type 7



Smurf1 and Smurf2

Smad ubiquitylation regulatory factors 1 and 2




Ubiquitin-conjugating catalytic fold


Ubiquitin C-terminal hydrolase


Ubiquitin C-terminal hydrolase 37


Ubiquitin C-terminal hydrolase 1


Ubiquitin–proteasome system


Ubiquitin-specific protease


Ubiquitin-specific protease 7


Ubiquitin-specific protease 25


Ubiquitin-specific protease 46


Valosin-containing protein



The work in the authors’ laboratory is funded by Fundação para a Ciência e a Tecnologia, Portugal (PTDC/SAU-GMG/101572/2008) and (PTDC/SAU-NMC/120144/2010), and M.S.B. received a scholarship from Fundação para a Ciência e Tecnologia (SFRH/BD/47963/2008). We thank Andreia Teixeira-Castro for critical review of the manuscript.


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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Márcio S. Baptista
    • 1
    • 2
  • Carlos B. Duarte
    • 3
    • 4
  • Patrícia Maciel
    • 1
    • 2
  1. 1.Life and Health Sciences Research Institute (ICVS), School of Health SciencesUniversity of Minho, Campus de GualtarBragaPortugal
  2. 2.PT Government Associate Laboratory, ICVS/3B’sBraga/GuimarãesPortugal
  3. 3.Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbraPortugal
  4. 4.Department of Life SciencesUniversity of CoimbraCoimbraPortugal

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