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在多个功能中被认为是促进的候选分子之一健康的衰老，因为它在几种与年龄相关的病理方面具有神经保护作用，并进行了几项研究在动物中完成的表现出Sirtuin 1与寿命伸长之间的关联。 Sirtuin 1已被证明影响几种脑部疾病，例如神经退行性疾病，例如阿尔茨海默氏病。因此，它重要的是要有一种用于非侵入性测量Sirtuin 1表达和功能的工具，而PET 成像将是理想的工具。不幸的是，迄今为止，还没有合适的非侵入性神经影像学工具来研究这些过程在动物或人类中，直到我们最近开发了Sirtuin 1的第一个PET成像探针。发展的发展可视化体内Sirtuin 1的技术代表了理解正常功能和 Sirtuin 1在大脑中的病理生理学。而且，这些技术将加速这些技术与Sirtuin 1相互作用的小分子疗法的发现/开发。该项目是旨在测量sirtuin 1在阿尔茨海默氏病动物模型和野生型小鼠大脑中的表达超过年龄，使用我们的新型PET成像探针[11C] CWL-1，在首次进行人类成像之前。