A role for SUMOylation in the formation and cellular localization of TDP-43 aggregates in amyotrophic lateral sclerosis

Cindy Maurel*, Anna A. Chami, Rose Anne Thépault, Sylviane Marouillat, Hélène Blasco, Philippe Corcia, Christian R. Andres, Patrick Vourc’h

*Corresponding author for this work

Research output: Contribution to journalArticle


In amyotrophic lateral sclerosis, motor neurons undergoing degeneration are characterized by the presence of cytoplasmic aggregates containing TDP-43 protein. SUMOylation, a posttranslational modification of proteins, has been previously implicated in the formation of aggregates positives for SOD1, another protein enriched in a subset of ALS patients. We show in this study that TDP-43 is also a target of SUMOylation. The inhibition of the first step of the SUMOylation process by anacardic acid significantly reduces the presence of TDP-43 aggregates and improves neuritogenesis and cell viability in vitro. Interestingly, the mutation of the unique SUMOylation site on TDP-43, using site-directed mutagenesis, modifies the intracellular localization of TDP-43 aggregates. Instead of being cytoplasmic where they are associated with toxic effects, they are located inside the nucleus. This change of localization results in improvement in cell viability and in global cellular functions. Our results implicate the SUMOylation site of TDP-43 in the formation of cytoplasmic TDP-43 aggregates, a hallmark of ALS, and thus identifies this region as a new target for novel therapeutic strategies.

Original languageEnglish
Pages (from-to)1361-1373
Number of pages13
JournalMolecular Neurobiology
Issue number3
Early online date15 Nov 2019
Publication statusPublished - Mar 2020
Externally publishedYes



  • Aggregation
  • ALS
  • SUMO
  • TDP-43

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