Sumoylation of critical proteins in amyotrophic lateral sclerosis: emerging pathways of pathogenesis

Neuromolecular Med. 2013 Dec;15(4):760-70. doi: 10.1007/s12017-013-8262-x. Epub 2013 Sep 24.


Emerging lines of evidence suggest a relationship between amyotrophic lateral sclerosis (ALS) and protein sumoylation. Multiple studies have demonstrated that several of the proteins involved in the pathogenesis of ALS, including superoxide dismutase 1, fused in liposarcoma, and TAR DNA-binding protein 43 (TDP-43), are substrates for sumoylation. Additionally, recent studies in cellular and animal models of ALS revealed that sumoylation of these proteins impact their localization, longevity, and how they functionally perform in disease, providing novel areas for mechanistic investigations and therapeutics. In this article, we summarize the current literature examining the impact of sumoylation of critical proteins involved in ALS and discuss the potential impact for the pathogenesis of the disease. In addition, we report and discuss the implications of new evidence demonstrating that sumoylation of a fragment derived from the proteolytic cleavage of the astroglial glutamate transporter, EAAT2, plays a direct role in downregulating the expression levels of full-length EAAT2 by binding to a regulatory region of its promoter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Amyotrophic Lateral Sclerosis / etiology*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • Astrocytes / metabolism
  • Calcium Signaling
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 2
  • Glutamate Plasma Membrane Transport Proteins / metabolism
  • Glutamic Acid / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Motor Neurons / metabolism
  • Muscular Disorders, Atrophic / metabolism
  • Nerve Tissue Proteins / physiology*
  • Protein Conformation
  • RNA-Binding Protein FUS / metabolism
  • Small Ubiquitin-Related Modifier Proteins / physiology*
  • Sumoylation / physiology*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1


  • DNA-Binding Proteins
  • Excitatory Amino Acid Transporter 2
  • Glutamate Plasma Membrane Transport Proteins
  • Nerve Tissue Proteins
  • RNA-Binding Protein FUS
  • SLC1A2 protein, human
  • SOD1 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Glutamic Acid
  • Superoxide Dismutase
  • Superoxide Dismutase-1