The role of the Cockayne syndrome protein

科凯恩综合征蛋白的作用

• 批准号: 10691065
• 负责人: Luigi Ferrucci
• 金额: $ 38.71万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10691065
• 关键词: Aging; Base Excision Repairs; Biological Models; Cachexia; Cockayne Syndrome; DNA Damage; DNA Repair; DNA Repair Pathway; Disease; Excision; Metabolism; Mitochondrial DNA; Mus; Mutation; Nerve Degeneration; Nuclear; Nucleotides; Oxidative Stress; Premature aging syndrome; Proteins; Role; Sampling; Supplementation; nicotinamide-beta-riboside; oxidative DNA damage; repaired; response

Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and is a segmental premature aging disorder. Mutations in CSA and CSB predominantly cause CS. There are deficiencies in the repair of oxidative DNA damage in both nuclear and mitochondrial DNA, and this may contribute to CS disease features. Previously, we demonstrated that the CSB protein interacts with PARP1, a protein involved in the early steps of DNA damage repair, and that these two proteins cooperate in the cellular responses to oxidative stress. PARP1 catabolizes NAD following DNA damage and we have shown that NAD I slower in CS mice samples. Further, we have shown that supplementation with nicotinamide riboside can mitigate some features of CS. We are continuing to investigate the role of CSA and CSB proteins in the multisystemic diseases associated with CS.

Cockayne综合征（CS）是一种以神经退行性变、恶病质为特征的常染色体隐性遗传疾病，是一种节段性早衰症。CSA和CSB的突变主要导致CS。在核和线粒体DNA中存在氧化DNA损伤修复的缺陷，这可能有助于CS疾病的特征。以前，我们证明了CSB蛋白与PARP1相互作用，PARP1是一种参与DNA损伤修复早期步骤的蛋白质，并且这两种蛋白质在细胞对氧化应激的反应中相互作用。PARP1在DNA损伤后分解代谢NAD，我们已经表明NAD I在CS小鼠样品中较慢。此外，我们已经表明，补充烟酰胺核苷可以减轻CS的一些特征。我们将继续研究CSA和CSB蛋白在与CS相关的多系统疾病中的作用。