S100-mediated signal transduction in the nervous system and neurological diseases.
S100-mediated signal transduction in the nervous system and neurological diseases.
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DOI：
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发表时间：
2005-09
影响因子：
1.6
通讯作者：
Zimmer Db;J. Chaplin;A. Baldwin;M. Rast
中科院分区：
文献类型：
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作者：
Zimmer Db;J. Chaplin;A. Baldwin;M. Rast
本文介绍了有关大脑中表达的 S100 家族成员的补体/水平的新信息，并回顾了大脑 S100 家族成员对神经系统功能和疾病的贡献。文献报道总共十个S100家族成员在脑中表达——S100A1、S100A2、S100A4、S100A5、S100A6、S100A10、S100A11、S100A13、S100B和S100Z。定量 Northern blot 分析在小鼠大脑中未检测到 S100A3、S100A8、S100A9 或 S100A14 mRNA，表明这些家族成员在大脑中不表达。此外，在小鼠大脑中检测到的六个家族成员的mRNA水平存在100倍的范围：S100A1/S100B水平比S100A6/S100A10水平高5倍，比S100A4/S100A13水平高100倍。这六个家族成员中的五个（S1100A1、S100A6、S100A10、S100A13 和 S100B）在成年小鼠中表现出年龄依赖性表达增加，范围为 5 至 20 倍。尽管之前关于 S100 在神经系统中功能的研究主要集中在 S100B，但其他家族成员（S100A1、S100A3、S100A4、S100A5）也与神经系统疾病有关。与 S100B 一样，这些家族成员的细胞内和细胞间形式与细胞生长、细胞分化和凋亡途径有关。本文介绍的研究表明，PC12 细胞中 S100A1 表达的消除会增加对 Abeta 肽诱导的细胞死亡的抵抗力，稳定细胞内 [Ca2+] 稳态，并减少淀粉样蛋白前体蛋白的表达。总而言之，这些结果证实了 S100 介导的信号转导途径在神经系统功能/疾病中发挥着重要作用，并表明 S100A1 与阿尔茨海默病中发生的神经元细胞功能障碍/死亡有关。
This article presents new information regarding the complement/level of S100 family members expressed in the brain and reviews the contribution of brain S100 family members to nervous system function and disease. A total of ten S100 family members are reported in the literature to be expressed in brain -S100A1, S100A2, S100A4, S100A5, S100A6, S100A10, S100A11, S100A13, S100B, and S100Z. Quantitative Northern blot analysis detected no S100A3, S100A8, S100A9 or S100A14 mRNA in mouse brain suggesting that these family members are not expressed in the brain. In addition, there was a 100-fold range in the mRNA levels for the six family members that were detected in mouse brain: S100A1/S100B levels were 5-fold higher than S100A6/S100A10 levels and 100-fold higher than S100A4/S100A13 levels. Five of these six family members (S1100A1, S100A6, S100A10, S100A13, and S100B) exhibited age-dependent increases in expression in adult mice that ranged from 5- to 20-fold. Although previous studies on S100 function in the nervous system have focused on S100B, other family members (S100A1, S100A3, S100A4, S100A5) have been implicated in neurological diseases. Like S100B, intra- and inter-cellular forms of these family members have been linked to cell growth, cell differentiation, and apoptotic pathways. Studies presented here demonstrate that ablation of S100A1 expression in PC12 cells results in increased resistance to Abeta peptide induced cell death, stabilization of intracellular [Ca2+] homeostasis, and reduced amyloid precursor protein expression. Altogether, these results confirm that S100-mediated signal transduction pathways play an important role in nervous system function/disease and implicate S100A1 in the neuronal cell dysfunction/death that occurs in Alzheimer's disease.