The brain lymphatic drainage system: structure, physiological functions, and pathological involvement in Parkinson’s disease

The brain lymphatic drainage system, a synergistic clearance axis consisting of the glymphatic system and meningeal lymphatic vessels, breaks the previous dogma that the lymphatic system is absent in the brain. The brain lymphatic drainage system has multiple physiological functions and is found to be related to Parkinson’s disease (PD) in both animal and human studies. α-synuclein (α-syn) protein, when misfolded, along with its post-translational modified forms plays a crucial role in PD, leading to the formation of cytotoxic oligomers and aggregates that result in neurodegeneration. There are reports showing that dysfunction of the brain lymphatic drainage system is associated with accumulation of α-syn and may be involved in neuroinflammation, immune disorder, and mitochondrial dysfunction, which are also pathogenic mechanisms of PD. However, the exact role of the brain lymphatic drainage system in PD pathogenesis remains unclear. This review systematically summarizes the structure of the brain lymphatic drainage system, its physiological functions, and pathological involvement in PD, and illustrates clinical imaging findings of PD. Finally, this review discusses the future directions that may help intervene in the brain lymphatic drainage system during the pathogenesis of PD.