Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Department of Physiology, University of California San Francisco, San Francisco, California, USA.
FASEB J. 2018 Feb;32(2):543-551. doi: 10.1096/fj.201700999. Epub 2018 Jan 3.
How solutes and macromolecules are removed from brain tissue is of central importance in normal brain physiology and in how toxic protein aggregates are cleared in neurodegenerative conditions, including Alzheimer's disease (AD). Conventionally, solute transport in the narrow and tortuous extracellular space in brain parenchyma has been thought to be primarily diffusive and nondirectional. The recently proposed "glymphatic" (glial-lymphatic) hypothesis posits that solute clearance is convective and driven by active fluid transport from para-arterial to paravenous spaces though aquaporin-4 water channels in astrocyte endfeet. Glymphatic, convective solute clearance has received much attention because of its broad implications for AD and other brain pathologies and even the function of sleep. However, the theoretical plausibility of glymphatic transport has been questioned, and recent data have challenged its experimental underpinnings. A substantiated mechanism of solute clearance in the brain is of considerable importance because of its implications for pathogenic mechanisms of neurologic diseases and delivery of therapeutics.-Smith, A. J., Verkman, A. S. The "glymphatic" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation?
溶质和生物大分子如何从脑组织中清除，这在正常脑生理学以及在神经退行性疾病（包括阿尔茨海默病，AD）中如何清除有毒蛋白聚集体方面具有核心重要性。传统上，人们认为脑实质中狭窄而曲折的细胞外空间中的溶质转运主要是扩散且无方向的。最近提出的“类淋巴系统”（神经胶质-淋巴系统）假说认为，通过星形细胞终足中的水通道蛋白-4 水通道，溶质清除是由从副动脉到静脉旁空间的主动流体转运驱动的，是对流的。由于其对 AD 和其他脑病理学甚至睡眠功能的广泛影响，类淋巴系统的对流性溶质清除受到了广泛关注。但是，类淋巴转运的理论可能性受到了质疑，最近的数据也对其实验基础提出了挑战。由于其对神经疾病发病机制和治疗药物输送的影响，大脑中溶质清除的合理机制非常重要。
