. Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes. Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):E4568-76. Epub 2014 Oct 14 PubMed.


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  1. The work by Pratt et al. is important because it strengthens the hypothesis that decreased stability of SOD1 mutants leads to cytotoxicity in ALS patients. However, a critical question remains unanswered in SOD1-linked ALS. Are aggregates of SOD1 mutants the cause of the toxicity, and do their formation kinetics impact the severity of disease, or are aggregates and toxicity unrelated consequences of a common root cause? Indeed, unfolded or misfolded SOD1 species, which have been observed in cell culture models, could play a role in the onset of the disease. Hopefully, further progress will be made when structural characterization—of either aggregated or misfolded SOD1—is carried out in the physiological environment of the cell.

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This paper appears in the following:


  1. Enzyme Structure Linked to ALS Severity

Research Models

  1. SOD1-G93A (hybrid) (G1H)