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

随年龄增长的阿尔茨海默病小鼠模型中去乙酰化酶 1 表达的研究

基本信息

批准号：
10407173
负责人：
Changning Wang
金额：
$ 32.38万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2024-05-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10407173
关键词：
Acetyltransferase Address Adenine Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease patient Amyotrophic Lateral Sclerosis Animal Disease Models Animal Model Animals Binding Brain Brain Diseases Bromodomain Cellular biology Central Nervous System Diseases Cessation of life Clinical Trials Coin Complex Couples DNA Sequence Data Dementia Development Differentiation and Growth Disease Disease Progression Drug abuse Elderly Electron Transport Enzymes Epigenetic Process FDA approved Family Functional disorder Genome Goals Growth and Development function Heart Diseases Histone Deacetylase Histones Human Huntington Disease Imaging Device Imaging Techniques In Vitro Investigation Investigative Techniques Kinetics Lead Life Longevity Lysine Malignant Neoplasms Measurement Measures Medical Research Metabolic Methods Modification Molecular Molecular Probes Mus Nature Neurodegenerative Disorders Niacinamide Parkinson Disease Pathologic Pathology Persons Pharmaceutical Preparations Physiological Play Positron-Emission Tomography Post-Translational Protein Processing Process Property Protein Family Proteins Reader Research Role SIRT1 gene Scientist Signal Transduction Sirtuins Specificity Tail Techniques Therapeutic Transgenic Animals United States Wild Type Mouse age related base biological adaptation to stress density design drug discovery effective therapy first-in-human healthy aging human imaging imaging agent imaging probe imaging study in vivo in vivo imaging interest man misfolded protein molecular imaging mouse model neuroimaging neuropathology non-invasive imaging novel novel therapeutics protein function sex small molecule therapeutics spinal and bulbar muscular atrophy technique development therapeutic development therapeutic target tool transcription factor uptake

项目摘要

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.

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已被证明影响几种脑部疾病，如神经退行性疾病，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。