Engine Failure in Axo-Myelinic Signaling: A Potential Key Player in the Pathogenesis of Multiple Sclerosis.
Engine Failure in Axo-Myelinic Signaling: A Potential Key Player in the Pathogenesis of Multiple Sclerosis.
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DOI：
10.3389/fncel.2021.610295
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发表时间：
2021
影响因子：
5.3
通讯作者：
Schenk GJ
中科院分区：
文献类型：
--
作者：
Bergaglio T;Luchicchi A;Schenk GJ
多发性硬化(MS)是一种复杂而慢性的中枢神经系统(CNS)疾病，以退行性和炎症性过程为特征，导致轴突损伤、脱髓鞘和神经元丢失。在过去的十年中，传统的由外向内的MS发病机制的观点已经受到了补充的自内向外理论的挑战，这种观点认为MS是一种主要的自身免疫性炎症病因。通过关注MS的退化过程，轴突-髓鞘系统可能会揭示疾病触发机制的新见解。氧化应激(OS)被广泛描述为包括MS在内的神经退行性疾病中导致组织损伤的手段之一。轴突线粒体是电活动轴突和神经元的主要能量来源，在很大程度上容易受到氧化损伤的影响。因此，轴突线粒体功能障碍可能损害有效的轴突-神经胶质通讯，进而影响轴突的完整性和轴突、神经元和突触信号的维持。在这篇综述文章中，我们认为OS来源的线粒体损伤可能强调轴突和它们的支持性神经胶质细胞之间的功能障碍，特别是少突胶质细胞，这一机制与初级细胞变性和次级促炎反应(由内向外)的发展有关，这反过来与可变启动的宿主免疫系统一起可能导致MS及其不同亚型的发生。
Multiple Sclerosis (MS) is a complex and chronic disease of the central nervous system (CNS), characterized by both degenerative and inflammatory processes leading to axonal damage, demyelination, and neuronal loss. In the last decade, the traditional outside-in standpoint on MS pathogenesis, which identifies a primary autoimmune inflammatory etiology, has been challenged by a complementary inside-out theory. By focusing on the degenerative processes of MS, the axo-myelinic system may reveal new insights into the disease triggering mechanisms. Oxidative stress (OS) has been widely described as one of the means driving tissue injury in neurodegenerative disorders, including MS. Axonal mitochondria constitute the main energy source for electrically active axons and neurons and are largely vulnerable to oxidative injury. Consequently, axonal mitochondrial dysfunction might impair efficient axo-glial communication, which could, in turn, affect axonal integrity and the maintenance of axonal, neuronal, and synaptic signaling. In this review article, we argue that OS-derived mitochondrial impairment may underline the dysfunctional relationship between axons and their supportive glia cells, specifically oligodendrocytes and that this mechanism is implicated in the development of a primary cytodegeneration and a secondary pro-inflammatory response (inside-out), which in turn, together with a variably primed host’s immune system, may lead to the onset of MS and its different subtypes.
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DOI：
10.1093/brain/aws012
发表时间：
2012-03
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Fischer MT;Sharma R;Lim JL;Haider L;Frischer JM;Drexhage J;Mahad D;Bradl M;van Horssen J;Lassmann H
通讯作者：
Lassmann H
影响因子：
14.5
作者：
DeLuca, GC;Ebers, GC;Esiri, MM
通讯作者：
Esiri, MM
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6.1
作者：
Guo C;Sun L;Chen X;Zhang D
通讯作者：
Zhang D
影响因子：
64.8
作者：
Fuenfschilling, Ursula;Supplie, Lotti M.;Mahad, Don;Boretius, Susann;Saab, Aiman S.;Edgar, Julia;Brinkmann, Bastian G.;Kassmann, Celia M.;Tzvetanova, Iva D.;Moebius, Wiebke;Diaz, Francisca;Meijer, Dies;Suter, Ueli;Hamprecht, Bernd;Sereda, Michael W.;Moraes, Carlos T.;Frahm, Jens;Goebbels, Sandra;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin