Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship.
Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship.
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DOI：
10.3390/metabo12030233
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发表时间：
2022-03-09
期刊：
影响因子：
4.1
通讯作者：
Valle C
中科院分区：
文献类型：
--
作者：
Candelise N;Salvatori I;Scaricamazza S;Nesci V;Zenuni H;Ferri A;Valle C
肌萎缩性侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是上肢和下肢运动神经元的进行性丧失。尽管人们在了解ALS的发病机制方面做出了越来越多的努力，但它仍然是一种不为人知的疾病，目前没有治疗方法可以阻止其进展。随着第一个与家族性ALS相关的基因——Cu-Zn超氧化物歧化酶的发现，线粒体显然是发病的关键因素。然而，随着越来越多的als相关基因被发现，人们的注意力从线粒体损伤转移到其他生物学功能，如蛋白质聚集和RNA代谢。近年来，由于越来越多的证据表明线粒体在ALS动物模型和患者中的紊乱，经常导致能量代谢失调，线粒体在病理中再次获得了核心的机制作用。在本文中，我们首先对als相关蛋白影响线粒体功能和细胞生物能量学的分子机制进行了最新研究。接下来，我们将重点关注从人类标本中收集的证据，并提出细胞特异性线粒体“代谢阈值”的概念，这可能在ALS发病机制中起关键作用。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of the upper and lower motor neurons. Despite the increasing effort in understanding the etiopathology of ALS, it still remains an obscure disease, and no therapies are currently available to halt its progression. Following the discovery of the first gene associated with familial forms of ALS, Cu–Zn superoxide dismutase, it appeared evident that mitochondria were key elements in the onset of the pathology. However, as more and more ALS-related genes were discovered, the attention shifted from mitochondria impairment to other biological functions such as protein aggregation and RNA metabolism. In recent years, mitochondria have again earned central, mechanistic roles in the pathology, due to accumulating evidence of their derangement in ALS animal models and patients, often resulting in the dysregulation of the energetic metabolism. In this review, we first provide an update of the last lustrum on the molecular mechanisms by which the most well-known ALS-related proteins affect mitochondrial functions and cellular bioenergetics. Next, we focus on evidence gathered from human specimens and advance the concept of a cellular-specific mitochondrial “metabolic threshold”, which may appear pivotal in ALS pathogenesis.
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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：
16.6
作者：
Altman T;Ionescu A;Ibraheem A;Priesmann D;Gradus-Pery T;Farberov L;Alexandra G;Shelestovich N;Dafinca R;Shomron N;Rage F;Talbot K;Ward ME;Dori A;Krüger M;Perlson E
通讯作者：
Perlson E
DOI：
10.1126/science.aaa3650
发表时间：
2015-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cirulli ET;Lasseigne BN;Petrovski S;Sapp PC;Dion PA;Leblond CS;Couthouis J;Lu YF;Wang Q;Krueger BJ;Ren Z;Keebler J;Han Y;Levy SE;Boone BE;Wimbish JR;Waite LL;Jones AL;Carulli JP;Day-Williams AG;Staropoli JF;Xin WW;Chesi A;Raphael AR;McKenna-Yasek D;Cady J;Vianney de Jong JM;Kenna KP;Smith BN;Topp S;Miller J;Gkazi A;FALS Sequencing Consortium;Al-Chalabi A;van den Berg LH;Veldink J;Silani V;Ticozzi N;Shaw CE;Baloh RH;Appel S;Simpson E;Lagier-Tourenne C;Pulst SM;Gibson S;Trojanowski JQ;Elman L;McCluskey L;Grossman M;Shneider NA;Chung WK;Ravits JM;Glass JD;Sims KB;Van Deerlin VM;Maniatis T;Hayes SD;Ordureau A;Swarup S;Landers J;Baas F;Allen AS;Bedlack RS;Harper JW;Gitler AD;Rouleau GA;Brown R;Harms MB;Cooper GM;Harris T;Myers RM;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
7.1
作者：
Cacabelos, Daniel;Ramirez-Nunez, Omar;Boada, Jordi
通讯作者：
Boada, Jordi
影响因子：
--
作者：
Cavallaro, Gabriele
通讯作者：
Cavallaro, Gabriele