The Skeleton of Lateral Meningocele Syndrome.
The Skeleton of Lateral Meningocele Syndrome.
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侧脑膜膨出综合征的骨骼。
DOI：
10.3389/fgene.2020.620334
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发表时间：
2020
影响因子：
3.7
通讯作者：
Canalis E
中科院分区：
文献类型：
--
作者：
Canalis E
Notch (Notch1 through 4) are transmembrane receptors that determine cell differentiation and function, and are activated following interactions with ligands of the Jagged and Delta-like families. Notch has been established as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages as well as in skeletal development and bone remodeling. Pathogenic variants of Notch receptors and their ligands are associated with a variety of genetic disorders presenting with significant craniofacial and skeletal manifestations. Lateral Meningocele Syndrome (LMS) is a rare genetic disorder characterized by neurological manifestations, meningoceles, skeletal developmental abnormalities and bone loss. LMS 与 NOTCH3 功能获得性致病变异相关。 Experimental mouse models of LMS revealed that the bone loss is secondary to increased osteoclastogenesis due to enhanced expression of receptor activator of nuclear factor kappa B ligand by cells of the osteoblast lineage. LMS 尚无有效疗法。 Antisense oligonucleotides targeting Notch3 and antibodies that prevent the activation of NOTCH3 are being tested in preclinical models of the disease.总之，LMS 是一种与 NOTCH3 致病变异相关的严重遗传性疾病。新颖的实验模型提供了对致病机制和纠正疾病的方法的见解。
Notch (Notch1 through 4) are transmembrane receptors that determine cell differentiation and function, and are activated following interactions with ligands of the Jagged and Delta-like families. Notch has been established as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages as well as in skeletal development and bone remodeling. Pathogenic variants of Notch receptors and their ligands are associated with a variety of genetic disorders presenting with significant craniofacial and skeletal manifestations. Lateral Meningocele Syndrome (LMS) is a rare genetic disorder characterized by neurological manifestations, meningoceles, skeletal developmental abnormalities and bone loss. LMS is associated with NOTCH3 gain-of-function pathogenic variants. Experimental mouse models of LMS revealed that the bone loss is secondary to increased osteoclastogenesis due to enhanced expression of receptor activator of nuclear factor kappa B ligand by cells of the osteoblast lineage. There are no effective therapies for LMS. Antisense oligonucleotides targeting Notch3 and antibodies that prevent the activation of NOTCH3 are being tested in preclinical models of the disease. In conclusion, LMS is a serious genetic disorder associated with NOTCH3 pathogenic variants. Novel experimental models have offered insight on mechanisms responsible and ways to correct the disease.
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影响因子：
9.8
作者：
Canalis, Ernesto
通讯作者：
Canalis, Ernesto
影响因子：
3.6
作者：
Bargman, Renee;Poshann, Ram;Pleshko, Nancy
通讯作者：
Pleshko, Nancy
影响因子：
2
作者：
Castori, Marco;Morlino, Silvia;Grammatico, Paola
通讯作者：
Grammatico, Paola
影响因子：
3.1
作者：
Albig, Allan R.;Becenti, Darryl J.;Schiemann, William P.
通讯作者：
Schiemann, William P.
影响因子：
4.8
作者：
Cordle, Jemima;Redfield, Christina;Handford, Penny A.
通讯作者：
Handford, Penny A.