Fig. 5.

The glymphatic system in tauopathies and α-synucleinopathies. During the development of these neurodegenerative diseases (purple arrows, left), it is believed that the glymphatic function and cytotoxic protein clearance become impaired, leading to the accumulation of aberrant proteins, further seeding and propagation, and destabilisation of the neuronal network, ultimately leading to disease progression. Recent studies suggest that manipulation of the glymphatic system (green arrows, right panel)—e.g. good sleep hygiene, leading a healthy lifestyle or the administration of osmotic drugs—may have the potential to increase glymphatic function and alleviate and reduce pathogenic accumulation of intracellular cytotoxic proteins. These plausible therapeutics have the potential to increase neuronal survival and therefore delay or even prevent the progression of disease. Protein accumulation (depicted by brown aggregates) as a result of the extent of glymphatic function in the two scenarios (appropriately weighted green arrows) is represented schematically in coronal diagrams of a degenerated (left) and healthy (right) human brain cross-section in the lower section of the figure