دورية أكاديمية
Prelamin A and ZMPSTE24 in premature and physiological aging
| العنوان: | Prelamin A and ZMPSTE24 in premature and physiological aging |
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| المؤلفون: | Howard J. Worman, Susan Michaelis |
| المصدر: | Nucleus, Vol 14, Iss 1 (2023) |
| بيانات النشر: | Taylor & Francis Group, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | Aging, farnesyl, Hutchinson–Gilford progeria syndrome, lamin, mandibuloacral dysplasia, nuclear envelope, Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | ABSTRACTAs human longevity increases, understanding the molecular mechanisms that drive aging becomes ever more critical to promote health and prevent age-related disorders. Premature aging disorders or progeroid syndromes can provide critical insights into aspects of physiological aging. A major cause of progeroid syndromes which result from mutations in the genes LMNA and ZMPSTE24 is disruption of the final posttranslational processing step in the production of the nuclear scaffold protein lamin A. LMNA encodes the lamin A precursor, prelamin A and ZMPSTE24 encodes the prelamin A processing enzyme, the zinc metalloprotease ZMPSTE24. Progeroid syndromes resulting from mutations in these genes include the clinically related disorders Hutchinson–Gilford progeria syndrome (HGPS), mandibuloacral dysplasia-type B, and restrictive dermopathy. These diseases have features that overlap with one another and with some aspects of physiological aging, including bone defects resembling osteoporosis and atherosclerosis (the latter primarily in HGPS). The progeroid syndromes have ignited keen interest in the relationship between defective prelamin A processing and its accumulation in normal physiological aging. In this review, we examine the hypothesis that diminished processing of prelamin A by ZMPSTE24 is a driver of physiological aging. We review features a new mouse (LmnaL648R/L648R) that produces solely unprocessed prelamin A and provides an ideal model for examining the effects of its accumulation during aging. We also discuss existing data on the accumulation of prelamin A or its variants in human physiological aging, which call out for further validation and more rigorous experimental approaches to determine if prelamin A contributes to normal aging. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 19491034 1949-1042 1949-1034 |
| العلاقة: | https://doaj.org/toc/1949-1034Test; https://doaj.org/toc/1949-1042Test |
| DOI: | 10.1080/19491034.2023.2270345 |
| الوصول الحر: | https://doaj.org/article/568632197e61423c87c184df6c837d5cTest |
| رقم الانضمام: | edsdoj.568632197e61423c87c184df6c837d5c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19491034 19491042 |
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| DOI: | 10.1080/19491034.2023.2270345 |