The structure and function of lamin A/C: Special focus on cardiomyopathy and therapeutic interventions

被引:5
作者
Tiwari, Vikas [1 ]
Alam, Md Jahangir [1 ,2 ]
Bhatia, Madhavi [1 ]
Navya, Malladi [1 ]
Banerjee, Sanjay K. [1 ]
机构
[1] Natl Inst Pharmaceut Educ & Res, Dept Biotechnol, Gauhati 781101, Assam, India
[2] CSIR, Indian Inst Chem Biol, Cell Biol & Physiol Div, Kolkata, India
关键词
Lamin A/C; Cardiomyopathy; Laminopathies; Genetic diseases; FAMILIAL DILATED CARDIOMYOPATHY; NUCLEAR-ENVELOPE; PROGERIA SYNDROME; MOUSE MODEL; LMNA-MUTATIONS; MANDIBULOACRAL DYSPLASIA; MOLECULAR ARCHITECTURE; MUSCULAR-DYSTROPHY; MISSENSE MUTATION; GENE-EXPRESSION;
D O I
10.1016/j.lfs.2024.122489
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Lamins are inner nuclear membrane proteins that belong to the intermediate filament family. Lamin A/C lie adjacent to the heterochromatin structure in polymer form, providing skeletal to the nucleus. Based on the localization, lamin A/C provides nuclear stability and cytoskeleton to the nucleus and modulates chromatin organization and gene expression. Besides being the structural protein making the inner nuclear membrane in polymer form, lamin A/C functions as a signalling molecule involved in gene expression as an enhancer inside the nucleus. Lamin A/C regulates various cellular pathways like autophagy and energy balance in the cytoplasm. Its expression is highly variable in differentiated tissues, higher in hard tissues like bone and muscle cells, and lower in soft tissues like the liver and brain. In muscle cells, including the heart, lamin A/C must be expressed in a balanced state. Lamin A/C mutation is linked with various diseases, such as muscular dystrophy, lipodystrophy, and cardiomyopathies. It has been observed that a good number of mutations in the LMNA gene impact cardiac activity and its function. Although several works have been published, there are still several unexplored areas left regarding the lamin A/C function and structure in the cardiovascular system and its pathological state. In this review, we focus on the structural organization, expression pattern, and function of lamin A/C, its interacting partners, and the pathophysiology associated with mutations in the lamin A/C gene, with special emphasis on cardiovascular diseases. With the recent finding on lamin A/C, we have summarized the possible therapeutic interventions to treat cardiovascular symptoms and reverse the molecular changes.
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页数:18
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