Brain-derived neurotrophic factor precursor in the immune system is a novel target for treating multiple sclerosis.
Brain-derived neurotrophic factor precursor in the immune system is a novel target for treating multiple sclerosis.
复制标题
免疫系统中的脑源性神经营养因子前体是治疗多发性硬化症的新靶点
作者：
Hu ZL;Luo C;Hurtado PR;Li H;Wang S;Hu B;Xu JM;Liu Y;Feng SQ;Hurtado-Perez E;Chen K;Zhou XF;Li CQ;Dai RP
原理：脑源性神经营养因子前体（proBDNF）在中枢神经系统（CNS）和免疫系统中表达。然而，proBDNF在多发性硬化症（MS）发病机制中的作用尚不清楚。研究方法：从多发性硬化患者获得外周血和死后脑和脊髓标本，以分析外周淋巴细胞和病变部位浸润免疫细胞中的proBDNF表达。在实验性自身免疫性脑脊髓炎（EAE）小鼠模型中检测proBDNF的表达谱，并采用多克隆和单克隆抗proBDNF抗体探讨其对EAE的治疗作用。最后，在体外实验中验证了proBDNF在外周血单个核细胞（PBMCs）的炎症免疫活性中的作用。结果如下：在MS患者脑和脊髓病变部位的循环淋巴细胞和浸润的炎性细胞中检测到高水平的proBDNF表达。在EAE小鼠模型中，proBDNF在CNS和循环及脾淋巴细胞中上调。全身而非颅内给予抗proBDNF阻断抗体可降低EAE小鼠的临床评分，限制脱髓鞘，并抑制促炎细胞因子。免疫刺激剂处理增加了proBDNF的释放，上调淋巴细胞中p75神经营养受体（p75NTR）的表达。针对proBDNF的单克隆抗体抑制PBMC在刺激后的炎症反应。结论：提示免疫细胞来源的proBDNF促进了MS的免疫发病机制，单克隆抗体proB有望成为治疗MS的有效药物。
Rationale: Brain-derived neurotrophic factor precursor (proBDNF) is expressed in the central nervous system (CNS) and the immune system. However, the role of proBDNF in the pathogenesis of multiple sclerosis (MS) is unknown. Methods: Peripheral blood and post-mortem brain and spinal cord specimens were obtained from multiple sclerosis patients to analyze proBDNF expression in peripheral lymphocytes and infiltrating immune cells in the lesion site. The proBDNF expression profile was also examined in the experimental autoimmune encephalomyelitis (EAE) mouse model, and polyclonal and monoclonal anti-proBDNF antibodies were used to explore their therapeutic effect in EAE. Finally, the role of proBDNF in the inflammatory immune activity of peripheral blood mononuclear cells (PBMCs) was verified in vitro experiments. Results: High proBDNF expression was detected in the circulating lymphocytes and infiltrated inflammatory cells at the lesion sites of the brain and spinal cord in MS patients. In the EAE mouse model, proBDNF was upregulated in CNS and in circulating and splenic lymphocytes. Systemic but not intracranial administration of anti-proBDNF blocking antibodies attenuated clinical scores, limited demyelination, and inhibited proinflammatory cytokines in EAE mice. Immuno-stimulants treatment increased the proBDNF release and upregulated the expression of p75 neurotrophic receptors (p75NTR) in lymphocytes. The monoclonal antibody against proBDNF inhibited the inflammatory response of PBMCs upon stimulations. Conclusion: The findings suggest that proBDNF from immune cells promotes the immunopathogenesis of MS. Monoclonal Ab-proB may be a promising therapeutic agent for treating MS.
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影响因子：
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作者：
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作者：
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