論文 - 詳細
| RRC ID | 45652 |
|---|---|
| 著者 | Vérièpe J, Fossouo L, Parker JA. |
| タイトル | Neurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neurons. |
| ジャーナル | Nat Commun |
| Abstract |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease thought to employ cell non-autonomous mechanisms where neuronal injury engages immune responses to influence disease progression. Here we show that the expression of mutant proteins causative for ALS in Caenorhabditis elegans motor neurons induces an innate immune response via TIR-1/Sarm1. Loss of function mutations in tir-1, associated downstream kinases, and the transcription factor atf-7 all suppress motor neuron degeneration. The neurosecretory proteins UNC-13 and UNC-31 are required for induction of the immune response as well as the degeneration of motor neurons. The human orthologue of UNC-13, UNC13A, has been identified as a genetic modifier of survival in ALS, and we provide functional evidence of UNC-13/UNC13A in regulating motor neuron degeneration. We propose that the innate immune system reacts to the presence of mutant proteins as a contagion, recruiting a pathogen resistance response that is ultimately harmful and drives progressive neurodegeneration. |
| 巻・号 | 6 |
| ページ | 7319 |
| 公開日 | 2015-6-10 |
| DOI | 10.1038/ncomms8319 |
| PII | ncomms8319 |
| PMID | 26059317 |
| MeSH | Amyotrophic Lateral Sclerosis / immunology Amyotrophic Lateral Sclerosis / pathology* Animals Animals, Genetically Modified Caenorhabditis elegans / immunology* Caenorhabditis elegans Proteins / immunology* Disease Models, Animal Immunity, Innate Motor Neurons / pathology Neurons / immunology* Receptors, G-Protein-Coupled / immunology* |
| IF | 12.121 |
| 引用数 | 28 |
| WOS 分野 | NEUROSCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 32 |
| 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 | tm2484 |