Protective roles of taurine in Alzheimer's disease brain

牛磺酸对阿尔茨海默病大脑的保护作用

基本信息

批准号：
10055586
负责人：
ALPASLAN DEDEOGLU
金额：
$ 233.73万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10055586
关键词：
Aging Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease pathology Amino Acids Amyloid beta-Protein Anti-Inflammatory Agents Area Autopsy Behavior Benign Brain Brain Diseases Brain region Complement Cysteine Data Development Diet Dietary Supplementation Disease Marker Disease Progression Dose Economic Burden Etiology Glial Fibrillary Acidic Protein Grant Hippocampus (Brain)Human Imaging Techniques In Vitro Incidence Inflammation Inflammatory Interleukin-1 Label Life Style Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measurement Measures Metabolic Metabolism Microglia Mus Neurons Osmoregulation Pathologic Pathology Report Pharmacology Plasma Play Population Positron-Emission Tomography Process Property Role Societies Specimen Stains Stroke Supplementation Symptoms Taurine Techniques Testing Therapeutic Effect Tissue Sample Tissues Traumatic Brain Injury age related neurodegeneration behavior test brain tissue cohort cytokine dietary supplements family burden imaging biomarker in vivo in vivo imaging inflammatory marker inflammatory modulation microPET mild cognitive impairment mouse model neurochemistry neuroinflammation neuropathology novel therapeutics prevent protective effect side effect theranostics translation to humans translational study uptake water maze

项目摘要

Abstract This project will examine the protective effects and mechanisms of dietary taurine supplementation in a mouse model of Alzheimer’s disease (AD). We will measure taurine uptake into the brain and taurine synthesis rates using labeled taurine and magnetic resonance spectroscopy (MRS). Then, we will determine how much protection taurine dietary supplementation (at various doses) provides against progression of Alzheimer’s disease (AD) symptoms in an AD mouse model. The protection will be measured using a battery of in vivo imaging markers (MRI, MRS, positron emission tomography (PET), behavioral tests and post mortem markers of neuroinflammation, AD pathology and neurochemistry (MRS) taken from the same mice. Then, the same post mortem measurements will be made in human brain tissue from a brain bank with very well characterized specimens including healthy controls, mild cognitive impairment and pathologically confirmed Alzheimer’s disease. The end result of the project should be a better understanding of the role of taurine in the brain and good test of a novel therapeutic that can also be detected in live human brain (a “theranostic”). This compound should be readily translatable to human populations due to its widespread use among athletes as a dietary supplement.

抽象的该项目将检查饮食牛磺酸的保护作用和机制在阿尔茨海默氏病小鼠模型中补充（AD）。我们将衡量使用标记的牛磺酸和磁共振光谱（MRS）。然后，我们将确定多少保护牛磺酸饮食补充（各种剂量）可反对 AD小鼠模型中阿尔茨海默氏病（AD）症状的进展。这将使用一组体内成像标记来测量保护（MRI，MRS，正电子发射断层扫描（PET），行为测试和验尸标记神经炎症，AD病理学和神经化学（MRS）从同一老鼠。然后，将在人脑中进行相同的验尸测量来自大脑库的组织，具有很好的标本，包括健康的标本对照，轻度认知障碍和病理确认的阿尔茨海默氏症疾病。该项目的最终结果应该更好地理解大脑中的牛磺酸和对新疗法的良好测试也可以在活人大脑（“疗法”）。该化合物应容易翻译成人类人口由于其在运动员中的广泛使用而作为饮食补充。