Brain Pericytes and the Progression of Alzheimer's Disease

大脑周细胞与阿尔茨海默病的进展

• 批准号: 10332753
• 负责人: Albert Louis Gonzales
• 金额: $ 25.41万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10332753
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Blood capillaries; Blood flow; Brain; Cardiovascular system; Cells; Centers of Research Excellence; Cerebral Amyloid Angiopathy; Erythrocytes; Health; Metabolic; Molecular; Nevada; Nutrient; Perfusion; Pericytes; Play; Role; Shapes; Signal Transduction; Smooth Muscle Myocytes; Testing; Tissues; Work; constriction; neuron loss; novel; wasting

To sustain the health of tissues in the body, the circulatory system needs to efficiently and continuously supply O2 and nutrients to every living cell in the brain, while also removing metabolic waste. Dr. Gonzales’s current work focuses on contractile pericytes located at capillary junctions and their role in regulating capillary blood flow. Contractile pericytes have multiple projections that wrap around capillaries and can regulate the passage of red blood cells (RBCs), but unlike bona fide arterial smooth muscle cells, a single pericyte is capable of compartmentalized contraction and constriction of different branches of a capillary junction. Dr. Gonzales’s recent work describes how pericytes play an important and novel role in structurally and dynamically modulating the shape of capillary junctions to insure the proper distribution of RBCs within the capillary network. The current proposal will test the hypothesis that amyloid-β, the major constituent of plaques in Alzheimer’s disease and cerebral amyloid angiopathy, disrupts or “short circuits” pericyte Ca2+ dynamics, leading to the eventual loss of junctional pericytes and an exponential decline in capillary perfusion efficiency, ultimately resulting in neuronal cell death.

为了维持身体组织的健康，循环系统需要高效和持续地向大脑中的每个活细胞供应氧气和营养物质，同时还需要清除代谢废物。冈萨雷斯博士目前的工作重点是位于毛细血管连接处的可收缩周细胞及其在调节毛细血管血流中的作用。收缩周细胞具有包裹在毛细血管周围的多个突起，可以调节红细胞(RBC)的通过，但与真正的动脉平滑肌细胞不同，单个周细胞能够区分收缩和收缩毛细血管连接的不同分支。Gonzales博士最近的工作描述了周细胞如何在结构上和动态地调节毛细血管连接的形状以确保红细胞在毛细血管网络中的正确分布中发挥重要而新颖的作用。目前的提议将检验这一假设，即阿尔茨海默病和脑淀粉样血管病斑块的主要成分淀粉样蛋白-β扰乱或“短路”周细胞钙动力学，导致连接周细胞最终丧失，毛细血管灌流效率指数下降，最终导致神经细胞死亡。