دورية أكاديمية
Lost in translation: a neglected mTOR target for lymphangioleiomyomatosis
العنوان: | Lost in translation: a neglected mTOR target for lymphangioleiomyomatosis |
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المؤلفون: | Jilly F. Evans, Francis X. McCormack, Nahum Sonenberg, Vera P. Krymskaya |
المصدر: | European Respiratory Review, Vol 32, Iss 169 (2023) |
بيانات النشر: | European Respiratory Society, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Diseases of the respiratory system |
مصطلحات موضوعية: | Diseases of the respiratory system, RC705-779 |
الوصف: | Lymphangioleiomyomatosis (LAM) is a cystic lung disease of women resulting from mutations in tuberous sclerosis complex (TSC) genes that suppress the mammalian target of rapamycin complex 1 (mTORC1) pathway. mTORC1 activation enhances a plethora of anabolic cellular functions, mainly via the activation of mRNA translation through stimulation of ribosomal protein S6 kinase (S6K1)/ribosomal protein S6 (S6) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1)/eukaryotic translation initiation factor 4E (eIF4E). Rapamycin (sirolimus), an allosteric inhibitor of mTORC1, stabilises lung function in many but not all LAM patients and, upon cessation of the drug, disease progression resumes. At clinically tolerable concentrations, rapamycin potently inhibits the ribosomal S6K1/S6 translation ribosome biogenesis and elongation axis, but not the translation 4E-BP1/eIF4E initiation axis. In this mini-review, we propose that inhibition of mTORC1-driven translation initiation is an obvious but underappreciated therapeutic strategy in LAM, TSC and other mTORC1-driven diseases. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 0905-9180 1600-0617 16000617 |
Relation: | http://err.ersjournals.com/content/32/169/230100.full; https://doaj.org/toc/0905-9180; https://doaj.org/toc/1600-0617 |
DOI: | 10.1183/16000617.0100-2023 |
URL الوصول: | https://doaj.org/article/b4061b3adcca44b1a7374c0f3bb2694c |
رقم الأكسشن: | edsdoj.b4061b3adcca44b1a7374c0f3bb2694c |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 09059180 16000617 |
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DOI: | 10.1183/16000617.0100-2023 |