Analysis of the functional effects of a mutation in SOD1 associated with familial amyotrophic lateral sclerosis
| Autor: | Maire E. Percy, Lorenzo Pinessi, D. R. Crapper McLachlan, Paul E. Fraser, W.G. Tatton, G. Vignocchi, Innocenzo Rainero, T. Tsuda, S. Munthasser, L Bergamini, Giovanna Vaula, P. St. George-Hyslop |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1994 |
| Předmět: |
Male
Cell type Molecular Sequence Data SOD1 Biology medicine.disease_cause Rats Sprague-Dawley Superoxide dismutase Immunoreactive protein Homologous chromosome medicine Animals Amino Acid Sequence Amyotrophic lateral sclerosis Molecular Biology Gene In Situ Hybridization Mutation Base Sequence General Neuroscience Amyotrophic Lateral Sclerosis medicine.disease Immunohistochemistry Molecular biology superoxide dismutase Rats nervous system familial amyotrophic lateral sclerosis Molecular Probes biology.protein |
| Popis: | Mutations in the Cu, Zn superoxide dismutase ( SOD1 ) gene have been reported in some pedigrees with Familial Amyotrophic Lateral Sclerosis (FALS). We have investigated the functional and structural effects of a Gly→Ser mutation at codon 41 of SOD1 in a pedigree with FALS and the topography of SOD 1 expression in the mammalian CNS. These analyses show that the 41 Gly→Ser mutation causes a 27% reduction in Cu, Zn SOD activity. SOD1 is transcribed at high levels in rat motoneurons and four other types of neurons homologous to upper motoneurons that degenerate in human ALS. However, SOD1 is transcribed at lower levels in other types of neurons, such as cerebellar Purkinje cells, which are not usually involved significantly in human ALS. On the other hand, immunocytochemical studies indicate that most types of rat neurons contain similar levels of Cu, Zn SOD immunoreactive protein. Nevertheless, these results suggest that the essential feature causing this subtype of ALS is either a reduction in Cu, Zn SOD activity in cell types that presumably critically require Cu, Zn SOD for protection against oxidative damage or the fact that the mutation in SOD1 associated with FALS results in a novel gain of function that is particularly deleterious to those cell types expressing SOD1 at high levels. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|