Interplay between the glymphatic system and neurotoxic proteins in Parkinson's disease and related disorders: current knowledge and future directions

Jan 16, 2024Neural regeneration research

How the brain’s waste clearance system relates to harmful proteins in Parkinson’s disease and similar disorders

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Abstract

Impairment of the glymphatic system may contribute to the progression of neurodegenerative diseases, including Parkinson's disease.

Parkinson's disease is characterized by the accumulation of neurotoxic proteins such as α-synuclein, amyloid-β, and tau.
The glymphatic system plays a crucial role in clearing these neurotoxic proteins from the brain.
Impairment of the glymphatic system could exacerbate protein aggregation and neuronal damage.
The review highlights the relationship between glymphatic system dysfunction and factors such as sleep, neuroinflammation, and astrogliosis.
Understanding these interactions may reveal new therapeutic strategies targeting glymphatic function in neurodegenerative diseases.

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Parkinson's disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins, including α-synuclein, amyloid-β, and tau, in addition to the impaired elimination of these neurotoxic protein. Atypical parkinsonism, which has the same clinical presentation and neuropathology as Parkinson's disease, expands the disease landscape within the continuum of Parkinson's disease and related disorders. The glymphatic system is a waste clearance system in the brain, which is responsible for eliminating the neurotoxic proteins from the interstitial fluid. Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease, as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage. Therefore, impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration. Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson's disease and related disorders; however, many unanswered questions remain. This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson's disease and related disorders. The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins, including loss of polarization of aquaporin-4 in astrocytic endfeet, sleep and circadian rhythms, neuroinflammation, astrogliosis, and gliosis. This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson's disease and related disorders, and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.

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Interplay between the glymphatic system and neurotoxic proteins in Parkinson's disease and related disorders: current knowledge and future directions

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