Aggregation of ubiquitin and a mutant ALS-linked SOD1 protein correlate with disease progression and fragmentation of the Golgi apparatus
| Autor: | Nicholas K. Gonatas, Anna Stieber, Jacqueline O. Gonatas |
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| Rok vydání: | 2000 |
| Předmět: |
animal diseases
SOD1 Golgi Apparatus Mice Transgenic Biology symbols.namesake Mice Ubiquitin Mutant protein medicine Neuropil Animals Ubiquitins Neurons Superoxide Dismutase Neurodegeneration Amyotrophic Lateral Sclerosis nutritional and metabolic diseases Motor neuron Golgi apparatus medicine.disease nervous system diseases Cell biology Microscopy Electron medicine.anatomical_structure nervous system Neurology Spinal Cord Cytoplasm Immunology symbols biology.protein Disease Progression Neurology (clinical) |
| Zdroj: | Journal of the neurological sciences. 173(1) |
| ISSN: | 0022-510X |
| Popis: | Transgenic mice that express the G93A mutation of human Cu,Zn superoxide dismutase (SOD1 G93A ), found in familial amyotrophic lateral sclerosis (FALS), showed clinical symptoms and histopathological changes of sporadic ALS, including fragmentation of the neuronal Golgi apparatus (GA). The finding of fragmented neuronal GA in asymptomatic mice, months before the onset of paralysis, suggests that the GA is an early target of the pathological processes causing neuronal degeneration. Transgenic mice expressing human SOD1 G93A have aggregates of mutant protein and ubiquitin in neuronal and glial cytoplasm; they appeared first in the neuropil and later in the perikarya of motor neurons, where they were adjacent to fragmented GA. The aggregates of SOD1 G93A appeared in neuronal perikarya of asymptomatic mice containing fragmented GA. The numbers of neurons with deposits of SOD1 G93A and fragmented GA progressively increased with age. Immuno-electron microscopy using colloidal gold showed labeling of ubiquitin and SOD1 over 13 nm thick cytoplasmic filaments. Spinal cord extracts showed a 20-fold increase of SOD1 G93A in transgenic mice compared to the wild-type protein in controls. The results suggest a causal relationship between the aggregation of mutant SOD1 and ubiquitin, fragmentation of the Golgi apparatus of motor neurons and neurodegeneration. |
| Databáze: | OpenAIRE |
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