The Role of the Glymphatic Clearance System in the Mechanisms of the Interactions of the Sleep–Waking Cycle and the Development of Neurodegenerative Processes

Selective and progressive neuron death is a characteristic feature of the neurodegenerative process and leads to corresponding neuron dysfunctions. Neurodegenerative diseases constitute a heterogeneous group of nosologies with different clinical presentations but similar molecular mechanisms of pathogenesis. They are based on processes of abnormal protein aggregation and the formation of fibrillar insoluble structures and their deposition as histopathological inclusions in nervous system tissues. Disruption of homeostatic functions regulating neuron ion and energy metabolism, protein and nucleotide biosynthesis and degradation, chronic hypoxia, and penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause age-related metabolic changes and disturbances in the sleep–waking cycle, but also contribute to the development of neurodegenerative processes. Animal studies have identified pathways of clearance in which solutes and specific tracers are cleared by a perivascular pathway into meningeal lymphatic vessels. The glymphatic network facilitates the clearance of metabolites, including beta-amyloid and tau protein, from the extracellular space of the brain. The glymphatic system is more efficient during natural sleep; fluid dynamics through this pathway display daily fluctuations and are under circadian control. The review systematizes the key aspects and scientific data from recent studies on the role of the glymphatic pathway and astroglial aquaporin type 4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, particularly in relation to the regulatory role of the sleep–waking cycle and during the development of neurodegenerative processes.