論文 - 詳細
| RRC ID | 76205 |
|---|---|
| 著者 | Kassouf T, Shrivastava R, Meszka I, Bailly A, Polanowska J, Trauchessec H, Mandrioli J, Carra S, Xirodimas DP. |
| タイトル | Targeting the NEDP1 enzyme to ameliorate ALS phenotypes through stress granule disassembly. |
| ジャーナル | Sci Adv |
| Abstract |
The elimination of aberrant inclusions is regarded as a therapeutic approach in neurodegeneration. In amyotrophic lateral sclerosis (ALS), mutations in proteins found within cytoplasmic condensates called stress granules (SGs) are linked to the formation of pathological SGs, aberrant protein inclusions, and neuronal toxicity. We found that inhibition of NEDP1, the enzyme that processes/deconjugates the ubiquitin-like molecule NEDD8, promotes the disassembly of physiological and pathological SGs. Reduction in poly(ADP-ribose) polymerase1 activity through hyper-NEDDylation is a key mechanism for the observed phenotype. These effects are related to improved cell survival in human cells, and in C. elegans, nedp1 deletion ameliorates ALS phenotypes related to animal motility. Our studies reveal NEDP1 as potential therapeutic target for ALS, correlated to the disassembly of pathological SGs. |
| 巻・号 | 9(13) |
| ページ | eabq7585 |
| 公開日 | 2023-3-31 |
| DOI | 10.1126/sciadv.abq7585 |
| PMID | 37000881 |
| PMC | PMC10065448 |
| MeSH | Amyotrophic Lateral Sclerosis* / drug therapy Amyotrophic Lateral Sclerosis* / genetics Animals Caenorhabditis elegans / genetics Humans Phenotype Stress Granules Ubiquitin |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 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 | tm1287 |