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，循环系统需要有效地持续为大脑中的每个活细胞提供氧气和营养物质，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收缩周细胞及其在调节毛细血管血流中的作用。收缩性周细胞具有多个突起，其缠绕在毛细血管周围并且可以调节红细胞（RBC）的通过，但与真正的动脉平滑肌细胞不同，单个周细胞能够区室化收缩和毛细血管连接的不同分支的收缩。冈萨雷斯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内的适当分布中发挥重要和新颖的作用。目前的建议将测试淀粉样蛋白-β，阿尔茨海默病和脑淀粉样血管病斑块的主要成分，破坏或“短路”周细胞Ca 2+动力学，导致连接周细胞的最终损失和毛细血管灌注效率的指数下降，最终导致神经元细胞死亡的假设。