New perspectives on the glymphatic system and the relationship between glymphatic system and neurodegenerative diseases
Yan-rui Sun, Qian-Kun Lv, Junyi Liu, Fen Wang, Chun‐Feng Liu
Abstract
Neurodegenerative diseases (ND) are characterized by the accumulation of aggregated proteins. The glymphatic system, through its rapid exchange mechanisms between cerebrospinal fluid (CSF) and interstitial fluid (ISF), facilitates the movement of metabolic substances within the brain, serving functions akin to those of the peripheral lymphatic system. This emerging waste clearance mechanism offers a novel perspective on the removal of pathological substances in ND. This article elucidates recent discoveries regarding the glymphatic system and updates relevant concepts within its model. It discusses the potential roles of the glymphatic system in ND, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple system atrophy (MSA), and proposes the glymphatic system as a novel therapeutic target for these conditions. • This work emphasizes the critical role of the myeloid niche within the perivascular space, a unique loose connective tissue structure essential for its functional dynamics. • It provides a detailed discussion and analysis of the functional mechanisms of CSF drainage via the dural sinus–meningeal lymphatic vessel system, shedding light on this emerging pathway. • The study comprehensively elucidates how oscillations in various brain components influence CSF circulation and ISF bulk flow dynamics, highlighting the interplay between neural and vascular activities. • Summarizes findings from the past five years linking the glymphatic system to clinical diagnosis and therapeutic approaches for neurodegenerative disorders, offering insights into potential advancements in treatment.