LENS PROTEIN ALPHA-CRYSTALLIN B CHAIN

PI正在继续研究aB的调节和功能- 晶状体蛋白是脊椎动物透镜的主要成分，也是 小的“热休克”蛋白质家族。 AB-晶状体蛋白在 CNS神经胶质和神经元在各种神经系统疾病中，在一些 实际上在神经胶质细胞中形成内含物的病例，如罗森塔尔 亚历山大病的纤维。 该基因的上调是为了响应 生理应激和蛋白质的作用是保护细胞免受 这些压力的不利后果，但监管模式 保护机制尚未完全了解。 来 上一个赠款期间，实验室已开始表征两个 不同的转录控制途径， 在受到生理应激的星形胶质细胞中调节表达， 一个通过热休克因子途径，一个通过热 冲击波非依赖性通路。 PI也开始探索如何 这种蛋白质对细胞具有保护作用。 他提出了一套 下一个赠款期的相互关联的具体目标，以进一步审查 aB-晶体基因的转录调控和 该蛋白在保护CNS细胞免受生理性损伤中的功能 应力 具体而言，他计划：1。 继续我们的研究， aB-晶状体蛋白基因在生理过程中的转录调控 应力 2. 进一步定义aB-stack如何保护电池免受 高渗和其他压力，3。 探索罗森塔尔的机制 纤维生产。

The PI is continuing studies on the regulation and function of aB- crystallin, a major component of the vertebrate lens and a member of the small "heat shock" protein family. AB-crystallin accumulates in CNS glia and neurons in a variety of neurological disorders, in some cases actually forming inclusions in glial cells, such as the Rosenthal fibers of Alexander disease. The gene is upregulated in response to physiological stresse and the protein serves to protect cells from the adverse consequences of those stresses, but the modes of regulation and the mechanisms of protection are not fully understood. Over the previous grant period, the laboratory has begun to characterize two different transcription controlpathways through which aB-crystallin expression is regulated in astrocytes subjected to physiological stresses, one through a heat shock factor pathway and one through a heat shock-independent pathway. The PI has also begun to explore how this protein confers protection upon cells. He proposes a set of interrelated specific aims for the next grant period to examine further the transcriptional regulation of the aB-crystalling gene and the function of the protein in protecting CNS cells from physiological stress. Specifically, he plans to: 1. continue our studies todefine the transcriptional regulation of the aB-crystallin gene during phsiological stress. 2. further define how aB-crystallinprotects cells from hypertonic and other stresses, 3. explore mechanisms of Rosenthal Fiber production.