The good, the bad, and the opportunities of the complement system in neurodegenerative disease.
The good, the bad, and the opportunities of the complement system in neurodegenerative disease.
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DOI：
10.1186/s12974-020-02024-8
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发表时间：
2020-11-25
影响因子：
9.3
通讯作者：
Tenner AJ
中科院分区：
文献类型：
--
作者：
Schartz ND;Tenner AJ
补体级联是先天免疫系统的一个关键效应机制，它有助于快速清除病原体和死亡或垂死细胞，并有助于炎症免疫反应的程度和限制。此外，该级联的一些早期成分已被清楚地证明在神经系统发育过程中对突触消除起有益作用，尽管在成人或受伤的大脑中过度补体介导的突触修剪可能对多种神经发生性疾病有害。虽然后来的许多研究都是在小鼠模型中进行的，但在人类死后脑组织检查中也报道了与这一观点一致的观察结果。C1q是经典补体通路的初始识别成分，它独立于补体级联的其余部分，并且与炎症的其他信号通路（在外周和中枢神经系统）的关系，人们对C1q的独特作用的认识日益增加，这突出了对这些分子实体和通路的全面理解的必要性，以促进成功的治疗设计，包括靶标识别。治疗的疾病分期和特定神经系统疾病的递送。在这里，我们回顾了补体成分和激活产物在多种神经退行性疾病中有益和有害作用的证据。本文回顾了各种后果的必要辅助因素的证据，以及最近的研究，这些研究支持成功的药理学方法抑制过度和有害的补体介导的慢性炎症的可能性，同时保留补体成分的有益作用，以减缓神经退行性疾病的进展。
The complement cascade is a critical effector mechanism of the innate immune system that contributes to the rapid clearance of pathogens and dead or dying cells, as well as contributing to the extent and limit of the inflammatory immune response. In addition, some of the early components of this cascade have been clearly shown to play a beneficial role in synapse elimination during the development of the nervous system, although excessive complement-mediated synaptic pruning in the adult or injured brain may be detrimental in multiple neurogenerative disorders. While many of these later studies have been in mouse models, observations consistent with this notion have been reported in human postmortem examination of brain tissue. Increasing awareness of distinct roles of C1q, the initial recognition component of the classical complement pathway, that are independent of the rest of the complement cascade, as well as the relationship with other signaling pathways of inflammation (in the periphery as well as the central nervous system), highlights the need for a thorough understanding of these molecular entities and pathways to facilitate successful therapeutic design, including target identification, disease stage for treatment, and delivery in specific neurologic disorders. Here, we review the evidence for both beneficial and detrimental effects of complement components and activation products in multiple neurodegenerative disorders. Evidence for requisite co-factors for the diverse consequences are reviewed, as well as the recent studies that support the possibility of successful pharmacological approaches to suppress excessive and detrimental complement-mediated chronic inflammation, while preserving beneficial effects of complement components, to slow the progression of neurodegenerative disease.
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DOI：
10.1177/1352458520924590
发表时间：
2021-04
期刊：
Multiple sclerosis (Houndmills, Basingstoke, England)
影响因子：
--
作者：
Bhargava P;Nogueras-Ortiz C;Kim S;Delgado-Peraza F;Calabresi PA;Kapogiannis D
通讯作者：
Kapogiannis D
影响因子：
5.3
作者：
Afagh, A;Cummings, BJ;Tenner, AJ
通讯作者：
Tenner, AJ
影响因子：
14
作者：
通讯作者：
--
影响因子：
4.2
作者：
Bellander, BM;Singhrao, SK;Svensson, M
通讯作者：
Svensson, M
影响因子：
5.3
作者：
Alawieh, Ali;Langley, E. Farris;Tomlinson, Stephen
通讯作者：
Tomlinson, Stephen