淋巴系统
陶氏病
水通道蛋白4
神经科学
细胞外
脑脊液
阿尔茨海默病
间质液
τ蛋白
间隙
病理
神经退行性变
化学
医学
疾病
心理学
生物化学
泌尿科
作者
Ian F. Harrison,Ozama Ismail,Asif Machhada,Niall Colgan,Yolanda Ohene,Payam Nahavandi,Zeshan Ahmed,Alice Fisher,S. Meftah,Tracey K. Murray,Ole Petter Ottersen,Erlend A. Nagelhus,Michael J. O’Neill,Jack A. Wells,Mark F. Lythgoe
出处
期刊:Brain
[Oxford University Press]
日期:2020-05-14
卷期号:143 (8): 2576-2593
被引量:343
标识
DOI:10.1093/brain/awaa179
摘要
Abstract The glymphatic system, that is aquaporin 4 (AQP4) facilitated exchange of CSF with interstitial fluid (ISF), may provide a clearance pathway for protein species such as amyloid-β and tau, which accumulate in the brain in Alzheimer’s disease. Further, tau protein transference via the extracellular space, the compartment that is cleared by the glymphatic pathway, allows for its neuron-to-neuron propagation, and the regional progression of tauopathy in the disorder. The glymphatic system therefore represents an exciting new target for Alzheimer’s disease. Here we aim to understand the involvement of glymphatic CSF-ISF exchange in tau pathology. First, we demonstrate impaired CSF-ISF exchange and AQP4 polarization in a mouse model of tauopathy, suggesting that this clearance pathway may have the potential to exacerbate or even induce pathogenic accumulation of tau. Subsequently, we establish the central role of AQP4 in the glymphatic clearance of tau from the brain; showing marked impaired glymphatic CSF-ISF exchange and tau protein clearance using the novel AQP4 inhibitor, TGN-020. As such, we show that this system presents as a novel druggable target for the treatment of Alzheimer’s disease, and possibly other neurodegenerative diseases alike.
科研通智能强力驱动
Strongly Powered by AbleSci AI