Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis.
Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis.
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作者：
Yousefian-Jazi A;Seol Y;Kim J;Ryu HL;Lee J;Ryu H
肌萎缩侧索硬化症（ALS）是最常见的运动神经元疾病和神经退行性疾病，影响上和/或下运动神经元。值得注意的是，它总是在发病后几年内导致死亡。虽然大多数ALS病例是散发性的，但家族性肌萎缩侧索硬化症（fALS）形成10%的病例。1993年，第一个fALS致病基因（SOD 1）被发现。随着遗传学的快速发展，迄今为止已经在ALS中发现了50多个潜在的致病或疾病修饰基因。因此，常规诊断测试应该包括最古老和最频繁突变的ALS基因以及ALS中的几个新的重要遗传变异。在此，我们讨论了目前的文献中的四个新发现的ALS相关基因（CYLD，S1 R，GLT 8D 1和KIF 5A）和以前众所周知的ALS基因，包括SOD 1，TARDBP，FUS和C9 orf 72。此外，我们还综述了这些基因的致病意义和疾病机制。阐明突变基因的细胞和分子功能将为治疗ALS的治疗方法的发展带来实质性的见解。
Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease and a neurodegenerative disorder, affecting the upper and/or lower motor neurons. Notably, it invariably leads to death within a few years of onset. Although most ALS cases are sporadic, familial amyotrophic lateral sclerosis (fALS) forms 10% of the cases. In 1993, the first causative gene (SOD1) of fALS was identified. With rapid advances in genetics, over fifty potentially causative or disease-modifying genes have been found in ALS so far. Accordingly, routine diagnostic tests should encompass the oldest and most frequently mutated ALS genes as well as several new important genetic variants in ALS. Herein, we discuss current literatures on the four newly identified ALS-associated genes (CYLD, S1R, GLT8D1, and KIF5A) and the previously well-known ALS genes including SOD1, TARDBP, FUS, and C9orf72. Moreover, we review the pathogenic implications and disease mechanisms of these genes. Elucidation of the cellular and molecular functions of the mutated genes will bring substantial insights for the development of therapeutic approaches to treat ALS.
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DOI：
10.1093/brain/awx370
发表时间：
2018-03-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Brenner D;Yilmaz R;Müller K;Grehl T;Petri S;Meyer T;Grosskreutz J;Weydt P;Ruf W;Neuwirth C;Weber M;Pinto S;Claeys KG;Schrank B;Jordan B;Knehr A;Günther K;Hübers A;Zeller D;Kubisch C;Jablonka S;Sendtner M;Klopstock T;de Carvalho M;Sperfeld A;Borck G;Volk AE;Dorst J;Weis J;Otto M;Schuster J;Del Tredici K;Braak H;Danzer KM;Freischmidt A;Meitinger T;Strom TM;Ludolph AC;Andersen PM;Weishaupt JH;German ALS network MND-NET
通讯作者：
German ALS network MND-NET
影响因子：
4.2
作者：
Borghero G;Pugliatti M;Marrosu F;Marrosu MG;Murru MR;Floris G;Cannas A;Occhineri P;Cau TB;Loi D;Ticca A;Traccis S;Manera U;Canosa A;Moglia C;Calvo A;Barberis M;Brunetti M;Gibbs JR;Renton AE;Errichiello E;Zoledziewska M;Mulas A;Qian Y;Din J;Pliner HA;Traynor BJ;Chiò A;ITALSGEN and SARDINALS Consortia
通讯作者：
ITALSGEN and SARDINALS Consortia
影响因子：
3.9
作者：
Abel, Olubunmi;Powell, John F.;Al-Chalabi, Ammar
通讯作者：
Al-Chalabi, Ammar
影响因子：
4
作者：
Ayala, Youhna M.;Zago, Paola;Baralle, Francisco E.
通讯作者：
Baralle, Francisco E.
影响因子：
11.2
作者：
Project MinE ALS Sequencing Consortium
通讯作者：
Project MinE ALS Sequencing Consortium