Status of treatment strategies for Hutchinson–Gilford progeria syndrome with a focus on prelamin: A posttranslational modification
| العنوان: | Status of treatment strategies for Hutchinson–Gilford progeria syndrome with a focus on prelamin: A posttranslational modification |
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| المؤلفون: | Xue Chen, Haidong Yao, Vicente Andrés, Martin O. Bergo, Muhammad Kashif |
| المصدر: | Basic & Clinical Pharmacology & Toxicology. 131:217-223 |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Pharmacology, Progeria, Adolescent, Farnesyltranstransferase, Humans, Nuclear Proteins, General Medicine, Lamin Type A, Toxicology, Protein Processing, Post-Translational |
| الوصف: | Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature ageing and early death at a mean age of 14.7 years. At the molecular level, HGPS is caused by a de novo heterozygous mutation in LMNA, the gene encoding A-type lamins (mainly lamin A and C) and nuclear proteins, which have important cellular functions related to structure of the nuclear envelope. The LMNA mutation leads to the synthesis of a truncated prelamin A protein (called progerin), which cannot undergo normal processing to mature lamin A. In normal cells, prelamin A processing involves four posttranslational processing steps catalysed by four different enzymes. In HGPS cells, progerin accumulates as a farnesylated and methylated intermediate in the nuclear envelope where it is toxic and causes nuclear shape abnormalities and senescence. Numerous efforts have been made to target and reduce the toxicity of progerin, eliminate its synthesis and enhance its degradation, but as of today, only the use of farnesyltransferase inhibitors is approved for clinical use in HGPS patients. Here, we review the main current strategies that are being evaluated for treating HGPS, and we focus on efforts to target the posttranslational processing of progerin. |
| تدمد: | 1742-7843 1742-7835 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d2efd9a2fa4d8407eacc229913a4430 https://doi.org/10.1111/bcpt.13770 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8d2efd9a2fa4d8407eacc229913a4430 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17427843 17427835 |
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