Investigation of sirtuin 1 expression in mice model of Alzheimer's disease over age

项目摘要 Sirtuin 1具有多种功能，被认为是促进细胞凋亡的候选分子之一。 健康老龄化，因为它对几种与年龄有关的病理学的神经保护作用， 在动物身上进行的一项研究表明，沉默调节蛋白1与寿命延长之间存在关联。Sirtuin 1已被证明 影响多种脑部疾病，例如神经退行性疾病，例如阿尔茨海默病。因此 重要的是要有一个工具，用于非侵入性测量沉默调节蛋白1的表达和功能，在体内， 成像将是一个理想的工具。 不幸的是，到目前为止，还没有合适的非侵入性神经影像学工具来研究这些过程 直到我们最近开发出第一个针对sirtuin 1的PET成像探针。的发展 用于在体内可视化sirtuin 1的技术代表了理解正常功能和 sirtuin 1在脑中的病理生理学。此外，这些技术将加速 发现/开发选择性地与sirtuin 1相互作用的小分子治疗剂。该项目 目的检测阿尔茨海默病动物模型和野生型小鼠脑中sirtuin 1的表达 在首次人体成像之前，使用我们的新型PET成像探头[11 C]CWL-1。

Project Summary Sirtuin 1 has been implicated in multiple functions is thought as one of the candidate molecules for promoting healthy aging, because of its neuroprotective roles against several age-related pathologies, and several studies done in animals showed an association between sirtuin 1 and lifespan elongation. Sirtuin 1 has been shown to impact several brain disorders such as neurodegenerative disorders, such as Alzheimer’s disease. Therefore, it is important to have a tool for non-invasive measurement of sirtuin 1 expression and function in vivo, and PET imaging would be an ideal tool. Unfortunately, to date, there are no suitable non-invasive neuroimaging tools for investigating these processes in animals or in man until we developed the first PET imaging probe for sirtuin 1 recently. The development of techniques for visualizing sirtuin 1 in vivo represents a key step in understanding both the normal function and pathophysiology of sirtuin 1 in brain. Moreover, these techniques these techniques will accelerate the discovery/development of small molecule therapeutics that selectively interacts with sirtuin 1. The project is aimed to measure the expression of sirtuin 1 in brain of Alzheimer’s Disease animal model and wild-type mice over age, using our novel PET imaging probe, [11C]CWL-1, prior to first-in-human imaging.