Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (9): 1973-1980.doi: 10.4103/1673-5374.390970

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

Yumei Yue1, Xiaodan Zhang2, Wen Lv1, Hsin-Yi Lai3, 4, 5, *, Ting Shen3, *   

  1. 1Department of Neurology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; 2Department of Emergency Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; 3Department of Neurology of the Second Affiliated Hospital and School of Brain Science and Brain Medicine, Interdisciplinary Institute of Neuroscience and Technology, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; 4College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, Zhejiang Province, China; 5MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
  • Online:2024-09-15 Published:2024-01-25
  • Contact: Ting Shen, PhD, shenting@zju.edu.cn; Hsin-Yi Lai, PhD, laihy@zju.edu.cn.
  • Supported by:
    This work was supported by the National Key R&D Program of China, No.2021YFF0702203 (to HYL); the National Natural Science Foundation of China, No. 82101323 (to TS); and Preferred Foundation of Zhejiang Postdoctors, No. ZJ2021152 (to TS).

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Abstract: 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.

Key words: atypical parkinsonism, glymphatic system, magnetic resonance imaging, neurotoxic proteins, Parkinson’s disease