The significance of the glymphatic pathway in the relationship between the sleep—wake cycle and neurodegenerative diseases

Oct 5, 2023Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova

The role of the brain’s waste clearance system in linking sleep patterns to neurodegenerative diseases

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Abstract

Neurodegenerative diseases may involve the abnormal aggregation of proteins leading to neuronal dysfunction.

Neurodegeneration is characterized by selective and progressive neuron death.
Common mechanisms include abnormal protein aggregation and formation of insoluble structures.
Homeostatic disturbances affecting neuronal metabolism and the entry of toxic substances are linked to neurodegenerative disease development.
In animal studies, specific pathways have been identified for the clearance of solutes from the brain.
The glymphatic pathway, which is regulated by sleep, helps remove metabolites like Aβ amyloid and tau protein.
Daily fluctuations in fluid dynamics through the glymphatic system are controlled by circadian rhythms.

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Selective and progressive death of neurons is a characteristic feature of the process of neurodegeneration and leads to corresponding neuronal dysfunctions. Neurodegenerative diseases represent a heterogeneous group of clinically distinct disorders with similar molecular mechanisms of pathogenesis. They are based on the processes of abnormal aggregation of proteins, the formation of fibrillary insoluble structures and their deposition in the form of histopathological inclusions in the tissues of the nervous system. Disturbance of homeostatic functions that regulate neuronal ion and energy metabolism, biosynthesis and degradation of proteins and nucleotides, chronic hypoxia and the penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause metabolic changes associated with age and disorders in the sleep-wake cycle, but also contribute to the development of neurodegenerative diseases. In animal studies, clearance pathways have been identified in which solutes and specific tracers are excreted perivascular into the meningeal lymphatics. The glymphatic pathway promotes the removal of metabolites, including Aβ amyloid and tau protein, from the parenchymal extracellular space of the brain. The glymphatic system is discussed to be more efficient during natural sleep, and fluid dynamics through this pathway exhibit daily fluctuations and are under circadian control. This review systematizes the key aspects and the data of recent research on the role of the glymphatic pathway and astroglial AQP-4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, in particular in relation to the regulatory role of the sleep-wake cycle and in development of neurodegeneration.

The significance of the glymphatic pathway in the relationship between the sleep—wake cycle and neurodegenerative diseases

Abstract

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