NGLY1 Deficiency, a Congenital Disorder of Deglycosylation: From Disease Gene Function to Pathophysiology.
NGLY1 Deficiency, a Congenital Disorder of Deglycosylation: From Disease Gene Function to Pathophysiology.
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DOI：
10.3390/cells11071155
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发表时间：
2022-03-29
期刊：
影响因子：
6
通讯作者：
Jafar-Nejad H
中科院分区：
文献类型：
--
作者：
Pandey A;Adams JM;Han SY;Jafar-Nejad H
N-聚糖酶 1 (NGLY1) 是一种胞质酶，参与去除错误折叠的 N-糖蛋白的 N 连接聚糖，被认为是内质网相关降解 (ERAD) 的组成部分。 2012 年，人们在一种罕见的多系统疾病中发现了隐性 NGLY1 突变，这引发了人们对 NGLY1 在动物发育和生理学中的作用以及 NGLY1 缺陷的病理生理学的深入研究。在这里，我们对 NGLY1 缺陷患者表型进行了回顾，并通过啮齿动物和无脊椎动物模型研究以及细胞培养和生化实验对该基因的功能进行了深入了解。我们将讨论受 NGLY1 丢失影响的关键过程，包括蛋白酶体反弹反应、线粒体功能和稳态以及骨形态发生蛋白 (BMP) 信号传导。我们还将介绍 NGLY1 的生物学相关靶标以及动物模型中 NGLY1 缺陷表型的遗传修饰剂。总之，这些发现和疾病模型为该疾病的潜在治疗方法的临床前测试提供了多种途径。
N-Glycanase 1 (NGLY1) is a cytosolic enzyme involved in removing N-linked glycans of misfolded N-glycoproteins and is considered to be a component of endoplasmic reticulum-associated degradation (ERAD). The 2012 identification of recessive NGLY1 mutations in a rare multisystem disorder has led to intense research efforts on the roles of NGLY1 in animal development and physiology, as well as the pathophysiology of NGLY1 deficiency. Here, we present a review of the NGLY1-deficient patient phenotypes, along with insights into the function of this gene from studies in rodent and invertebrate animal models, as well as cell culture and biochemical experiments. We will discuss critical processes affected by the loss of NGLY1, including proteasome bounce-back response, mitochondrial function and homeostasis, and bone morphogenetic protein (BMP) signaling. We will also cover the biologically relevant targets of NGLY1 and the genetic modifiers of NGLY1 deficiency phenotypes in animal models. Together, these discoveries and disease models have provided a number of avenues for preclinical testing of potential therapeutic approaches for this disease.
跨线粒体疾病病因和组织的综合转录组分析提高了对呼吸链功能障碍的常见细胞适应性的理解。
DOI：
10.1016/j.biocel.2014.02.012
发表时间：
2014-05
影响因子：
4
作者：
Zhang, Zhe;Falk, Marni J.
通讯作者：
Falk, Marni J.