"Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord" Benjamin G Trist, Sian Genoud, Stéphane Roudeau, Alexander Rookyard, Amr Abdeen, Veronica Cottam, Dominic J. Hare, Melanie White, Jens Altvater, Jennifer A. Fifita, Alison Hogan, Natalie Grima, Ian P. Blair, Kai Kysenius, Peter J. Crouch, Asuncion Carmona, Yann Rufin, Stéphane Claverol, Stijn Van Malderen, Gerald Falkenberg, David J. Paterson, Bradley Smith, Claire Troakes, Caroline Vance, Christopher E. Shaw, Safa Al-Sarraj, Stuart Cordwell, Glenda Halliday, Richard Ortega, Kay L. Double Brain, 2022 https://doi.org/10.1093/brain/awac165

Abnormal superoxide dismutase-1 (SOD1) protein has been widely examined in cellular and animal models of amyotrophic lateral sclerosis (ALS), where it is shown to contribute to the death of spinal cord cells that normally control movement. Detailed examination of this protein in spinal cord tissues from ALS patients, however, remains scarce. Without such data, it is difficult to fully understand how abnormal SOD1 protein contributes to the loss of spinal cord cells in ALS patients, hindering the development of treatments which aim to counteract abnormal forms of this protein. We utilized tissues from ALS patients to investigate how this protein is abnormal in ALS, finding that it is not only failing to perform its normal function in the spinal cord of ALS patients, but that it is also abnormal in structure and location within spinal cord cells that degenerate in this disorder. These changes were associated with alterations to the amount of metals bound to the protein, which normally serve to stabilize it and enable its function, as well as with the presence of atypical chemical modifications to the protein, which actively change the protein’s structure. These changes were only found in regions of the spinal cord experiencing cell loss and were not present in healthy control patients, who lack significant spinal cord cell loss, suggesting a contribution to cellular degeneration in ALS patients. Our data reinforce the involvement of abnormal SOD1 protein in cellular loss in the ALS spinal cord, and identify potential mechanisms by which we may counteract abnormal forms of this protein in ALS patients.

View article