論文 - 詳細
| RRC ID | 6436 |
|---|---|
| 著者 | Wang J, Farr GW, Hall DH, Li F, Furtak K, Dreier L, Horwich AL. |
| タイトル | An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. |
| ジャーナル | PLoS Genet |
| Abstract |
The nature of toxic effects exerted on neurons by misfolded proteins, occurring in a number of neurodegenerative diseases, is poorly understood. One approach to this problem is to measure effects when such proteins are expressed in heterologous neurons. We report on effects of an ALS-associated, misfolding-prone mutant human SOD1, G85R, when expressed in the neurons of Caenorhabditis elegans. Stable mutant transgenic animals, but not wild-type human SOD1 transgenics, exhibited a strong locomotor defect associated with the presence, specifically in mutant animals, of both soluble oligomers and insoluble aggregates of G85R protein. A whole-genome RNAi screen identified chaperones and other components whose deficiency increased aggregation and further diminished locomotion. The nature of the locomotor defect was investigated. Mutant animals were resistant to paralysis by the cholinesterase inhibitor aldicarb, while exhibiting normal sensitivity to the cholinergic agonist levamisole and normal muscle morphology. When fluorescently labeled presynaptic components were examined in the dorsal nerve cord, decreased numbers of puncta corresponding to neuromuscular junctions were observed in mutant animals and brightness was also diminished. At the EM level, mutant animals exhibited a reduced number of synaptic vesicles. Neurotoxicity in this system thus appears to be mediated by misfolded SOD1 and is exerted on synaptic vesicle biogenesis and/or trafficking. |
| 巻・号 | 5(1) |
| ページ | e1000350 |
| 公開日 | 2009-1-1 |
| DOI | 10.1371/journal.pgen.1000350 |
| PMID | 19165329 |
| PMC | PMC2621352 |
| MeSH | Animals Animals, Genetically Modified Bacterial Proteins / metabolism Caenorhabditis elegans / physiology* Gene Expression Regulation* Humans Luminescent Proteins / metabolism Mice Models, Biological Models, Genetic Mutation* Neurons / metabolism* Protein Folding RNA Interference Superoxide Dismutase / genetics* Synapses / metabolism* |
| IF | 5.175 |
| 引用数 | 104 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm903 |