THE ROLE OF GAP JUNCTIONS IN OXIDATIVE NEURODEGENERATION IN CEREBELLUM

间隙连接在小脑氧化性神经变性中的作用

• 批准号: 7960191
• 负责人: DINGBO D LIN
• 金额: $ 7.53万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960191
• 关键词: Age of Onset; Apoptosis; Biomedical Research; Cells; Cerebellum; Computer Retrieval of Information on Scientific Projects Database; Connexins; Defect; Funding; Gap Junctions; Grant; Human; Institution; Kansas; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Oxidative Stress; Play; Process; Purkinje Cells; Research; Research Personnel; Resources; Role; Source; Spinocerebellar Ataxias; Transgenic Mice; United States National Institutes of Health; mouse model; mutant; overexpression; protein kinase C gamma; relating to nervous system; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gap junctions play important roles in cerebellar neurodegeneration. Protein kinase C gamma (PKCgamma) is a neuronal specific PKC. Activated PKCgamma phosphorylates and inhibits gap junctions, a process which is controlled by a cell oxidative state. Mutations in PKCgamma cause spinocerebellar ataxia type 14 (SCA-14), an autosomal, dominant neurodegenerative disorder in humans with onset ages of three to thirty years. In this proposal we will determine how gap junctions are controlled by PKCgamma activation and what the effect of inhibition of gap junctions on neural apoptosis. We will also characterize the defects in cerebellar response to oxidative stress in the PKCgamma H101Y SCA14 transgenic mouse models. Overexpression of the PKCgamma H101Y SCA14 mutation leads to significant loss of Purkinje cells in transgenic mice due to improper control of gap junctions by PKCgamma mutants.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 缝隙连接在小脑神经退行性变中起重要作用。蛋白激酶C γ（PKC γ）是一种神经元特异性PKC。活化的PKC γ磷酸化并抑制间隙连接，这是一个由细胞氧化状态控制的过程。PKC γ突变导致脊髓小脑共济失调14型（SCA-14），这是一种常染色体显性遗传的神经退行性疾病，发病年龄为3至30岁。在这个提议中，我们将确定缝隙连接是如何被PKC γ激活控制的，以及缝隙连接的抑制对神经细胞凋亡的影响。我们还将表征PKC γ H101 Y SCA 14转基因小鼠模型中小脑对氧化应激反应的缺陷。 PKC γ H101 Y SCA 14突变的过表达导致转基因小鼠中浦肯野细胞的显著损失，这是由于PKC γ突变体对间隙连接的不当控制。