Role of vascular KATP channels in Alzheimer’s neurodegeneration and dementia

摘要 我们努力的一个主要焦点是了解 心血管系统中的ATP敏感钾离子通道。有相互矛盾的报道称 KATP通道参与阿尔茨海默病(AD)的发病机制，我们假设这是 这是因为不同的通道参与了神经元而不是脑血管。我们建议 特异性阻断血管中的KATP通道将是有益的，我们建议在AD中测试这一点 通过对心血管KATP通道的精确遗传操作来建立模型小鼠。如果成功，这些研究将 为在动物模型中测试CS治疗的相关药理学方法奠定了基础 在人类身上，最终目标是开发一种针对CS和相关病理的特定疗法。

Abstract A major focus of our efforts is to understand the mechanistic basis and functional consequences of ATPsensitive potassium (KATP) ion channels in the cardiovascular system. There are contradictory reports of KATP channel involvement in Alzheimer's Disease (AD) pathogenesis, and we hypothesize that this is because of the involvement of different channels in neurons versus in cerebral blood vessels. We propose that blocking KATP channels in blood vessels specifically will be beneficial, and we propose to test this in AD model mice by precise genetic manipulation of cardiovascular KATP channels. If successful, these studies will form the background to the testing of relevant pharmacological approaches to CS therapy in animal models and in humans, with the ultimate goal of developing a specific therapy for CS and related pathologies.