Targeting S100B in Cerebral Ischemia and in Alzheimer's Disease.
Targeting S100B in Cerebral Ischemia and in Alzheimer's Disease.
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DOI：
10.1155/2010/687067
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Town, Terrence
中科院分区：
文献类型：
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作者：
Mori, Takashi;Asano, Takao;Town, Terrence
S100 B是一种EF-手型钙结合蛋白，对多种细胞过程发挥细胞内和细胞外作用。该蛋白质主要在中枢神经系统中由星形胶质细胞表达，在生理学上和在神经系统疾病过程中都是如此。在健康成人大脑和发育过程中，组成性S100 B表达作为一种营养因子驱动神经突起延伸和裁判神经可塑性。然而，当在中枢神经系统疾病期间被诱导时，该蛋白质可以发挥适应不良的作用，从而加剧大脑病理学。基于遗传学和药理学的证据，我们认为S100 B在两种常见的大脑病理中的有害作用：缺血性中风和阿尔茨海默病（AD）。在缺血性脑损伤的啮齿动物模型中，S100 B在亚急性期早期被诱导，在亚急性期它加剧神经胶质增生和延迟梗死扩展，从而阻碍功能恢复。在AD小鼠模型中，S100 B驱动大脑炎症和神经胶质增生，加速大脑淀粉样变性。S100 B合成的药理学抑制减轻了这两种脑部疾病的标志性病理，为治疗这些破坏性神经系统疾病的转化方法打开了大门。
S100B is an EF-hand calcium-binding protein that exerts both intracellular and extracellular effects on a variety of cellular processes. The protein is predominantly expressed in the central nervous system by astrocytes, both physiologically and during the course of neurological disease. In the healthy adult brain and during development, constitutive S100B expression acts as a trophic factor to drive neurite extension and to referee neuroplasticity. Yet, when induced during central nervous system disease, the protein can take on maladaptive roles and thereby exacerbate brain pathology. Based on genetic and pharmacological lines of evidence, we consider such deleterious roles of S100B in two common brain pathologies: ischemic stroke and Alzheimer's disease (AD). In rodent models of ischemic brain damage, S100B is induced early on during the subacute phase, where it exacerbates gliosis and delayed infarct expansion and thereby worsens functional recovery. In mouse models of AD, S100B drives brain inflammation and gliosis that accelerate cerebral amyloidosis. Pharmacological inhibition of S100B synthesis mitigates hallmark pathologies of both brain diseases, opening the door for translational approaches to treat these devastating neurological disorders.