The role of gonadotropins in regulating the production of Alzheimer's beta amyloid

促性腺激素在调节阿尔茨海默病β淀粉样蛋白产生中的作用

• 批准号: nhmrc : 426406
• 负责人: A/Pr Giuseppe Verdile
• 金额: $ 26.69万
• 依托单位: Edith Cowan University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2008
• 资助国家: 澳大利亚
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-gonadotropins-regulating-beta-amyloid/97516
• 关键词: role; gonadotropins; regulating; production; Alzheimer

Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause or testosterone during andropuase, has been associated with the increased risk of developing AD and in altering the levels of beta amyloid. Furthermore, menopause and andropause are also characterised by changes in other reproductive hormones such as the gonadotropins. High levels of the gonadotropins have also been associated with the increased risk of developing AD. Therefore it is important to identify how these changes modify the risk of developing AD. This study examines the role of the gonadotropins in regulating beta amyloid levels in cell culture and in an animal model for AD. Furthermore, this study will assess, in the animal model, the use of gonadotropin lowering agents to reduce levels of beta amyloid. The results from this study will provide important data on how reproductive hormones regulate beta amyloid. Further insight into these mechanisms will provide therapeutic or preventative strategies for AD.

目前，约有16万澳大利亚人患有痴呆症；其中50-70%是阿尔茨海默病（AD）病例。阿尔茨海默病的临床表现为记忆和人格改变，病理表现为淀粉样蛋白沉积。在阿尔茨海默病的发病机制中，一种叫做-淀粉样蛋白的小分子尤为重要，这种小分子的过量产生被认为是阿尔茨海默病发展的核心。生殖激素水平的变化，特别是绝经期雌激素水平的降低或雄激素酶期间睾丸激素水平的降低，与阿尔茨海默病发病风险的增加和β -淀粉样蛋白水平的改变有关。此外，更年期和男性更年期还以其他生殖激素如促性腺激素的变化为特征。高水平的促性腺激素也与患AD的风险增加有关。因此，确定这些变化如何改变患AD的风险是很重要的。本研究探讨了促性腺激素在细胞培养和AD动物模型中调节β -淀粉样蛋白水平的作用。此外，本研究将在动物模型中评估使用促性腺激素降低剂来降低β -淀粉样蛋白水平。这项研究的结果将为生殖激素如何调节-淀粉样蛋白提供重要数据。进一步了解这些机制将为阿尔茨海默病提供治疗或预防策略。