Mechanisms of Neurotoxicity in Parkinson's Disease

帕金森病的神经毒性机制

• 批准号: 7296359
• 负责人: EIRENE KONTOPOULOS
• 金额: $ 3.06万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7296359
• 关键词: Drosophilidae; Parkinson' s disease; alpha synuclein; arthropod genetics; cell death; gene mutation; immunocytochemistry; neurons; neurotoxicology; parkin gene /protein; pathologic process; predoctoral investigator; protein protein interaction; sectioning

DESCRIPTION (provided by applicant): Our long-term objective is to elucidate the underlying mechanisms of neuronal death in Parkinson's disease (PD). The identification of several genes exhibiting linkage to PD has not yet led to the understanding of how their protein products bring about cell death. Though in vitro studies have been instrumental in identifying potential mechanisms of neurodegeneration, their findings need to be corroborated in vivo. I propose to utilize Drosophila genetics to investigate putative protein interactions among three PD-linked genes: synphilin-1, alpha-synuclein, and parkin. My primary strategy will be to investigate the inherent toxicity of synphilin-1 and its PD-associated mutation, R621C. Furthermore, genetic interactions between both forms of synphilin and either alpha-synuclein or parkin will be examined. These efforts will culminate in the investigation of genetic interactions among synphilin-1, alpha-synuclein, and parkin.

描述（由申请人提供）：我们的长期目标是阐明帕金森病（PD）神经元死亡的潜在机制。几个与 PD 相关的基因的鉴定尚未导致人们了解它们的蛋白质产物如何导致细胞死亡。尽管体外研究有助于确定神经退行性变的潜在机制，但他们的发现需要在体内得到证实。我建议利用果蝇遗传学来研究三个 PD 相关基因之间假定的蛋白质相互作用：synphilin-1、α-synuclein 和 Parkin。我的主要策略是研究 synphilin-1 及其 PD 相关突变 R621C 的固有毒性。此外，还将检查两种形式的突触蛋白与α-突触核蛋白或parkin之间的遗传相互作用。这些努力最终将导致对 synphilin-1、α-synuclein 和 Parkin 之间遗传相互作用的研究。