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Updated: May 7, 2026

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
Sumoylation of critical proteins in amyotrophic lateral sclerosis: emerging pathways of pathogenesis
Emily Foran1, Lauren Rosenblum, Alexey I Bogush
1Frances and Joseph Weinberg Unit for ALS Research, Department of Neuroscience, Farber Institute for Neuroscience, Thomas Jefferson University, 900 Walnut Street, JHN Bldg., Philadelphia, PA, 19107, USA.
Abstract:
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.
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