論文 - 詳細
| RRC ID | 84084 |
|---|---|
| 著者 | Siddiqui AA, Merquiol E, Bruck-Haimson R, Hirbawi J, Boocholez H, Cohen I, Yan Y, Dong MQ, Blum G, Cohen E. |
| タイトル | Cathepsin B promotes Aβ proteotoxicity by modulating aging regulating mechanisms. |
| ジャーナル | Nat Commun |
| Abstract |
While the activities of certain proteases promote proteostasis and prevent neurodegeneration-associated phenotypes, the protease cathepsin B (CTSB) enhances proteotoxicity in Alzheimer's disease (AD) model mice, and its levels are elevated in brains of AD patients. How CTSB exacerbates the toxicity of the AD-causing Amyloid β (Aβ) peptide is controversial. Using an activity-based probe, aging-altering interventions and the nematode C. elegans, we discovered that the CTSB CPR-6 promotes Aβ proteotoxicity but mitigates the toxicity of polyQ stretches. While the knockdown of cpr-6 does not affect lifespan, it alleviates Aβ toxicity by reducing the expression of swsn-3 and elevating the level of the protein SMK-1, both involved in the regulation of aging. These observations unveil a mechanism by which CTSB aggravates Aβ-mediated toxicity, indicate that it plays opposing roles in the face of distinct proteotoxic insults and highlight the importance of tailoring specific remedies for distinct neurodegenerative disorders. |
| 巻・号 | 15(1) |
| ページ | 8564 |
| 公開日 | 2024-10-3 |
| DOI | 10.1038/s41467-024-52540-x |
| PII | 10.1038/s41467-024-52540-x |
| PMID | 39362844 |
| PMC | PMC11450018 |
| MeSH | Aging* / genetics Aging* / metabolism Alzheimer Disease* / genetics Alzheimer Disease* / metabolism Alzheimer Disease* / pathology Amyloid beta-Peptides* / metabolism Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cathepsin B* / genetics Cathepsin B* / metabolism Disease Models, Animal |
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オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 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 | tm12210 |