The role of reticulons in neurodegenerative diseases.
The role of reticulons in neurodegenerative diseases.
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DOI：
10.1007/s12017-013-8271-9
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发表时间：
2014-03
影响因子：
3.5
通讯作者：
Orlacchio, Antonio
中科院分区：
文献类型：
--
作者：
Chiurchiu, Valerio;Maccarrone, Mauro;Orlacchio, Antonio
网状细胞（Reticulons，RTNs）是一组膜相关蛋白，主要负责形成管状内质网网络、膜运输、抑制轴突生长和细胞凋亡。这些蛋白质有一个共同的序列特征，即网状蛋白同源结构域，它由成对的疏水性片段组成，据信这些片段通过在双层膜中充当楔形物来诱导膜弯曲。RTN在所有组织中普遍表达，但每个RTN成员都表现出独特的表达模式，偏好某些组织甚至细胞类型。最近，越来越多的证据表明RTNs还有其他意想不到的作用，包括DNA结合、自噬和一些炎症相关功能。RTNs的这些多方面作用说明了它们参与神经退行性疾病如阿尔茨海默病、肌萎缩性侧索硬化症、多发性硬化症以及遗传性痉挛性截瘫的日益增长的认识。本文综述了RTNs在人类病理生理学中的最新发现，以及这些RTNs在神经退行性疾病中的作用，沿着这些发现对更好地理解RTNs引发的分子事件及其作为下一代治疗药物的潜在开发的影响。
Reticulons (RTNs) are a group of membrane-associated proteins mainly responsible for shaping the tubular endoplasmic reticulum network, membrane trafficking, inhibition of axonal growth, and apoptosis. These proteins share a common sequence feature, the reticulon homology domain, which consists of paired hydrophobic stretches that are believed to induce membrane curvature by acting as a wedge in bilayer membranes. RTNs are ubiquitously expressed in all tissues, but each RTN member exhibits a unique expression pattern that prefers certain tissues or even cell types. Recently, accumulated evidence has suggested additional and unexpected roles for RTNs, including those on DNA binding, autophagy, and several inflammatory-related functions. These manifold actions of RTNs account for their ever-growing recognition of their involvement in neurodegenerative diseases like Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as hereditary spastic paraplegia. This review summarizes the latest discoveries on RTNs in human pathophysiology, and the engagement of these in neurodegeneration, along with the implications of these findings for a better understanding of the molecular events triggered by RTNs and their potential exploitation as next-generation therapeutics.
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