Fig. 1.

Hypothetical outline of the folding and aggregation pathways of SOD1 and how these can be linked to neurotoxicity in ALS. CCS, copper chaperone for SOD1. The EM image of the SOD1 fibrils is adapted from the article of Chattopadhyay et al. (5) in this issue of PNAS, and the fibrillar propensities of the SOD1 sequence as predicted by WALZ are shown in blue. It remains now to find out whether SOD1 fibrillation is linked to neurotoxicity and deposition of proteinaceous inclusions, along the same lines as have been implicated for other neurodegenerative diseases.