Marshak D R
Cold Spring Harbor Laboratory, NY 11724.
Prog Brain Res. 1990;86:169-81.
S100 beta is a multifunctional protein that is found in large amounts in astrocytes and a number of other tissues. In the developing nervous system, S100 beta is secreted from proliferating astrocytes during the time of neurite outgrowth from cortical neurons. The secreted form has neurotrophic activity on primary neurons and neuroblastoma cells. The neurotrophic activity is sensitive to reduction of disulfide bonds, and appears to be a disulfide dimer of S100 beta. The accumulation of S100 beta in mature glial cells is associated with microtubule network. The transfection and expression of cDNA for S100 beta in mammalian cells confers neurotrophic activity on extracts of these cells. Based on our observations of a neurotrophic activity for S100 beta, the occurrence of the gene for S100 beta on human chromosome 21 (Allore et al., 1988) and the elevated levels of S100 beta-containing cells in AD and DS brains (Griffin et al., 1989), we suggest that S100 beta plays a role in the abnormal development of the nervous system in DS and the degeneration of central neurons in AD. It is essential at the present stage to demonstrate the action of S100 beta in vivo, and to construct animal models, such as transgenic mice, that overexpress S100 beta. Such models will allow the dissection of the role of S100 beta in the developing and degenerating central nervous system.
S100β是一种多功能蛋白质，在星形胶质细胞和许多其他组织中大量存在。在发育中的神经系统中，S100β在皮质神经元神经突生长期间从增殖的星形胶质细胞中分泌出来。分泌形式对原代神经元和神经母细胞瘤细胞具有神经营养活性。这种神经营养活性对二硫键的还原敏感，似乎是S100β的二硫键二聚体。成熟胶质细胞中S100β的积累与微管网络有关。S100β的cDNA在哺乳动物细胞中的转染和表达赋予这些细胞提取物神经营养活性。基于我们对S100β神经营养活性的观察、S100β基因在人类21号染色体上的存在（Allore等人，1988年）以及阿尔茨海默病（AD）和唐氏综合征（DS）大脑中含S100β细胞水平的升高（Griffin等人，19S9年），我们认为S100β在DS神经系统的异常发育以及AD中枢神经元的退化中起作用。现阶段至关重要的是证明S100β在体内的作用，并构建过表达S100β的动物模型，如转基因小鼠。这样的模型将有助于剖析S100β在发育中和退化中的中枢神经系统中的作用。
