摘要
人体静脉输注免疫球蛋白(IVIG) 主要是治疗自身免疫神经紊乱及许多神经退行性疾病的一种潜在制剂,有各种各样的潜在治疗机制,如:T细胞运输调节、细胞因子、Fc受体阻塞及补体激活级联的打断。在阿尔默茨病中,IVIG呈现了抗β-淀粉样蛋白(Aβ)聚合物的天然抗体,因此IVIG免疫治疗也可能增强对Aβ的清除,保护大脑功能;IVIG尤其可以调节补体产物过敏霉素如:C5a 和 C3,过敏霉素在AD 小鼠模型中脑内AMPA 和 NMDA受体表达调节 、AMPA-PKA-CREB信号通路进一步上调及突触功能方面有重要作用。补体成分的向下调节与年龄相关的痴呆症认知功能衰退及随着年龄增长先天免疫力下降有关联。IVIG免疫治疗通过其对脑内C3, C5a 成分水平的局部调节,有可能成为引人注目的新颖的AD治疗剂。
关键词: 阿尔默茨病,认知功能,补体成分,免疫治疗,IVIG,突触可塑性
Current Alzheimer Research
Title:Role of Complement Systems in IVIG Mediated Attenuation of Cognitive Deterioration in Alzheimer's Disease
Volume: 11 Issue: 7
Author(s): Bing Gong, Samara Levine, Scott R. Barnum and Giulio M. Pasinetti
Affiliation:
关键词: 阿尔默茨病,认知功能,补体成分,免疫治疗,IVIG,突触可塑性
摘要: Human intravenous immunoglobulin (IVIG) has been indicated as a potential therapy for autoimmune neurological disorders, as well as in many neurodegenerative diseases, with various underlying therapeutic mechanisms such as regulation of T-cell trafficking, cytokines, Fc receptor blocking, and interruption of complement activation cascade. In Alzheimer’s disease (AD), IVIG presents naturally occurring antibodies against amyloid-beta (Aβ) aggregation, thus IVIG immunotherapy may increase the clearance of Aβ and protect brain function. Recently, we and others reported that besides Aβ clearance, IVIG specifically regulates the levels of complement-derived anaphylatoxins, such as C5a and C3, which play an important role in the regulation of AMPA and NMDA receptor expression in the brain and further upregulate the AMPA-PKA-CREB signaling pathway and synaptic function in AD mouse models. Since down-regulation of complement components has been linked with deficits of cognitive function in age-related dementia following the decline of innate immunity during aging, the IVIG immunotherapy could be an attractive novel AD therapeutic through its local regulation of C3, C5a component levels in brain.
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Cite this article as:
Gong Bing, Levine Samara, R. Barnum Scott and Pasinetti M. Giulio, Role of Complement Systems in IVIG Mediated Attenuation of Cognitive Deterioration in Alzheimer's Disease, Current Alzheimer Research 2014; 11 (7) . https://dx.doi.org/10.2174/1567205011666140812113707
DOI https://dx.doi.org/10.2174/1567205011666140812113707 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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