Browsing by Author "White, M"
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- ItemAltered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord(Oxford University Press, 2022-09-09) Trist, BG; Genoud, S; Roudeau, S; Rookyard, A; Abdeen, A; Cottam, V; Hare, DJ; White, M; Altvater, J; Fifita, JA; Hogan, A; Grima, N; Blair, Ian P; Kysenius, Kai; Crouch, Peter J; Carmona, A; Rufin, Y; Claverol, S; Van Malderen, S; Falkenberg, G; Paterson, DJ; Smith, B; Troakes, C; Vance, C; Shaw, CE; Al-Sarraj, S; Cordwell, S; Halliday, G; Ortega, R; Double, KLAberrant self-assembly and toxicity of wild-type and mutant superoxide dismutase 1 (SOD1) has been widely examined in silico, in vitro and in transgenic animal models of amyotrophic lateral sclerosis. Detailed examination of the protein in disease-affected tissues from amyotrophic lateral sclerosis patients, however, remains scarce. We used histological, biochemical and analytical techniques to profile alterations to SOD1 protein deposition, subcellular localization, maturation and post-translational modification in post-mortem spinal cord tissues from amyotrophic lateral sclerosis cases and controls. Tissues were dissected into ventral and dorsal spinal cord grey matter to assess the specificity of alterations within regions of motor neuron degeneration. We provide evidence of the mislocalization and accumulation of structurally disordered, immature SOD1 protein conformers in spinal cord motor neurons of SOD1-linked and non-SOD1-linked familial amyotrophic lateral sclerosis cases, and sporadic amyotrophic lateral sclerosis cases, compared with control motor neurons. These changes were collectively associated with instability and mismetallation of enzymatically active SOD1 dimers, as well as alterations to SOD1 post-translational modifications and molecular chaperones governing SOD1 maturation. Atypical changes to SOD1 protein were largely restricted to regions of neurodegeneration in amyotrophic lateral sclerosis cases, and clearly differentiated all forms of amyotrophic lateral sclerosis from controls. Substantial heterogeneity in the presence of these changes was also observed between amyotrophic lateral sclerosis cases. Our data demonstrate that varying forms of SOD1 proteinopathy are a common feature of all forms of amyotrophic lateral sclerosis, and support the presence of one or more convergent biochemical pathways leading to SOD1 proteinopathy in amyotrophic lateral sclerosis. Most of these alterations are specific to regions of neurodegeneration, and may therefore constitute valid targets for therapeutic development. © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/bync/ 4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
- ItemA new Cretaceous fossil mammal locality from the Bass Coast of southeastern Australia(Taylor & Francis, 2022-10-20) Rich, TH; Lowery, M; Hall, M; Kool, L; Bevitt, J; White, M; Vickers-Rich, PMesozoic mammals from the polar regions of Australian Gondwana are exceptionally rare. The recovery of a partial jaw attributable to the australosphenid Ausktribosphenos nyktos from a new locality along the Bass Coast of Victoria is, therefore, significant because it comes from an uppermost Barremian to lowermost Aptian grit with abundant plant material that differs lithologically from other previously productive laminated sandstone deposits. We interpret this as evidence for a floodplain habitat that was distant from local water bodies. The identification of a new Cretaceous mammal locality in Australia highlights the exciting prospects for future fossil discoveries. © 2024 Informa UK Limited