SOD1-positive aggregate accumulation in the CNS predicts slower disease progression and increased longevity in a mutant SOD1 mouse model of ALS
Autor: | Cindy Gill, Theo Hatzipetros, Beth Levine, Valerie R. Tassinari, Monica Z. Wang, Joshua D. Kidd, Marcel Maier, Alan Gill, Fernando G. Vieira, Andrew Moreno, James P. Phelan, Jan Grimm, Kenneth Thompson |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Protein Folding Transgene media_common.quotation_subject animal diseases SOD1 Longevity lcsh:Medicine Mice Transgenic Disease Biology Neuroprotection Article Pathogenesis Superoxide dismutase 03 medical and health sciences 0302 clinical medicine Superoxide Dismutase-1 medicine Animals Amyotrophic lateral sclerosis lcsh:Science media_common Multidisciplinary lcsh:R Amyotrophic Lateral Sclerosis nutritional and metabolic diseases medicine.disease Immunohistochemistry Mice Mutant Strains nervous system diseases Disease Models Animal 030104 developmental biology nervous system Spinal Cord Cancer research biology.protein lcsh:Q Female Protein aggregation 030217 neurology & neurosurgery |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) |
ISSN: | 2045-2322 |
Popis: | Non-natively folded variants of superoxide dismutase 1 (SOD1) are thought to contribute to the pathogenesis of familial amyotrophic lateral sclerosis (ALS), however the relative toxicities of these variants are controversial. Here, we aimed to decipher the relationships between the different SOD1 variants (aggregated, soluble misfolded, soluble total) and the clinical presentation of ALS in the SOD1G93A mouse. Using a multi-approach strategy, we found that the CNS regions least affected by disease had the most aggregated SOD1. We also found that the levels of aggregated SOD1 in the spinal cord were inversely correlated with the disease progression. Conversely, in the most affected regions, we observed that there was a high soluble misfolded/soluble total SOD1 ratio. Taken together, these findings suggest that soluble misfolded SOD1 may be the disease driver in ALS, whereas aggregated SOD1 may serve to sequester the toxic species acting in a neuroprotective fashion. |
Databáze: | OpenAIRE |
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