LENS PROTEIN ALPHA-CRYSTALLIN B CHAIN

PI正在继续研究AB-的调节和功能。 晶体蛋白，脊椎动物晶状体的主要成分，也是 小“热休克”蛋白家族。AB-晶状体蛋白在 中枢神经系统胶质细胞和神经元在各种神经疾病中，在一些 实际在神经胶质细胞中形成包涵体的病例，如Rosenthal 亚历山大病的纤维。该基因上调是为了应对 生理压力和蛋白质用来保护细胞免受 这些压力的不利后果，但监管模式 而且保护机制还没有完全被理解。超过了 在之前的资助期内，实验室已经开始表征两个 AB-晶状体蛋白的不同转录调控途径 在生理应激条件下，星形胶质细胞的表达受到调节， 一种通过热休克因子途径，另一种通过热 休克非依赖性途径。公安局也开始探索如何 这种蛋白质为细胞提供保护。他提出了一套 下一个赠款期间的相互关联的具体目标，以进一步审查 AB结晶性基因的转录调控与细胞周期调控 蛋白质在保护中枢神经系统细胞免受生理性损伤中的作用 压力。具体地说，他计划：1.继续我们的研究，以确定 AB-晶体蛋白基因在生理过程中的转录调控 压力。2.进一步定义AB-晶体蛋白如何保护细胞免受 高渗等应激，3.探讨罗森塔尔的发病机制 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.