Optic neuropathies: the tip of the neurodegeneration iceberg.
Optic neuropathies: the tip of the neurodegeneration iceberg.
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DOI：
10.1093/hmg/ddx273
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发表时间：
2017-10-01
影响因子：
3.5
通讯作者：
Sadun AA
中科院分区：
文献类型：
--
作者：
Carelli V;La Morgia C;Ross-Cisneros FN;Sadun AA
视神经和它的120万个轴突的起源细胞，视网膜神经节细胞(RGC)，特别容易受到与线粒体功能障碍有关的神经退化的影响。视神经疾病的范围可能从非综合征遗传性实体，到罕见的具有视神经萎缩的综合征多系统疾病，如线粒体脑肌病，再到与年龄相关的神经退行性疾病，如阿尔茨海默氏症和帕金森氏病，直到最近，视神经受累一直是一个相对被忽视的特征。新的工具可以用来彻底研究视神经功能，允许无与伦比的进入中枢神经系统的这一部分。了解RGC神经退行性变和视神经萎缩的分子病理生理学机制，对于广泛了解神经退行性疾病的发病机制，监测其进展情况，描述自然历史，并最终作为评估治疗结果的指标是关键。在这篇综述中，从分子到解剖学的不同层面，可能导致RGC神经变性和视神经萎缩的不同层面被综合地处理，考虑到所有相关的参与者。这些包括RGC树突、细胞体和轴突、无髓视网膜神经纤维层和有髓鞘板层后轴突，以及溶解的突触细胞和星形胶质细胞，以寻找非常规功能。功能失调的线粒体动力学、转运、有丝分裂的动态平衡控制和有丝分裂的去除，以及特定的凋亡倾向，可能针对不同的细胞类型和解剖环境。最终，我们可以设想新的研究方法和治疗方案，以加快神经退行性疾病的早期诊断和治愈。
The optic nerve and the cells that give origin to its 1.2 million axons, the retinal ganglion cells (RGCs), are particularly vulnerable to neurodegeneration related to mitochondrial dysfunction. Optic neuropathies may range from non-syndromic genetic entities, to rare syndromic multisystem diseases with optic atrophy such as mitochondrial encephalomyopathies, to age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease where optic nerve involvement has, until recently, been a relatively overlooked feature. New tools are available to thoroughly investigate optic nerve function, allowing unparalleled access to this part of the central nervous system. Understanding the molecular pathophysiology of RGC neurodegeneration and optic atrophy, is key to broadly understanding the pathogenesis of neurodegenerative disorders, for monitoring their progression in describing the natural history, and ultimately as outcome measures to evaluate therapies. In this review, the different layers, from molecular to anatomical, that may contribute to RGC neurodegeneration and optic atrophy are tackled in an integrated way, considering all relevant players. These include RGC dendrites, cell bodies and axons, the unmyelinated retinal nerve fiber layer and the myelinated post-laminar axons, as well as olygodendrocytes and astrocytes, looked for unconventional functions. Dysfunctional mitochondrial dynamics, transport, homeostatic control of mitobiogenesis and mitophagic removal, as well as specific propensity to apoptosis may target differently cell types and anatomical settings. Ultimately, we can envisage new investigative approaches and therapeutic options that will speed the early diagnosis of neurodegenerative diseases and their cure.
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影响因子：
3.7
作者：
Coppola G;Di Renzo A;Ziccardi L;Martelli F;Fadda A;Manni G;Barboni P;Pierelli F;Sadun AA;Parisi V
通讯作者：
Parisi V
影响因子：
11.2
作者：
Carelli, Valerio;Musumeci, Olimpia;Caporali, Leonardo;Zanna, Claudia;La Morgia, Chiara;Del Dotto, Valentina;Porcelli, Anna Maria;Rugolo, Michela;Valentino, Maria Lucia;Iommarini, Luisa;Maresca, Alessandra;Barboni, Piero;Carbonelli, Michele;Trombetta, Costantino;Valente, Enza Maria;Patergnani, Simone;Giorgi, Carlotta;Pinton, Paolo;Rizzo, Giovanni;Tonon, Caterina;Lodi, Raffaele;Avoni, Patrizia;Liguori, Rocco;Baruzzi, Agostino;Toscano, Antonio;Zeviani, Massimo
通讯作者：
Zeviani, Massimo
影响因子：
--
作者：
Baracca, A;Solaini, G;Carelli, V
通讯作者：
Carelli, V
影响因子：
4.1
作者：
Balducci, Nicole;Savini, Giacomo;Barboni, Piero
通讯作者：
Barboni, Piero
影响因子：
4.6
作者：
Borrelli, Enrico;Triolo, Giacinto;Barboni, Piero
通讯作者：
Barboni, Piero