中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (9): 1973-1980.doi: 10.4103/1673-5374.390970

• 综述:退行性病与再生 • 上一篇    下一篇

脑类淋巴系统与神经毒性蛋白在帕金森病及相关疾病间的互作

  

  • 出版日期:2024-09-15 发布日期:2024-01-25

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).

摘要:

帕金森病是一种常见的神经退行性疾病,与神经毒性蛋白(包括α-突触核蛋白、淀粉样蛋白-β(Aβ)和Tau)的异常聚集沉积以及清除障碍有关。非典型帕金森病与帕金森病具有相同的临床表现和神经病理学。脑类淋巴系统是大脑中的废物清除系统,负责清除间质中的神经毒性蛋白。脑类淋巴系统受损加剧了神经毒性蛋白聚集、造成神经元丢失,是导致神经退行性疾病发生和发展的重要因素,可能是神经退行性疾病的共同损伤途径。近年来针对脑类淋巴系统损伤在神经退行性疾病中的研究逐渐成为热点,这一热点在帕金森病及相关疾病中的研究情况有待更新和总结。文章首先介绍了脑类淋巴系统的解剖结构组成及功能影响因素。然后,总结了帕金森病及相关疾病脑类淋巴系统受损情况、神经毒性蛋白沉积,重点讨论了脑类淋巴系统与神经毒性蛋白相互作用的机制,并对帕金森病及相关疾病以脑类淋巴系统为靶标进行治疗的展望。了解脑类淋巴系统的功能,及在帕金森病及相关疾病发生中的机制,以期更有助于疾病预后判断和治疗策略的制定。

https://orcid.org/0000-0002-3937-4427 (Ting Shen); https://orcid.org/0000-0001-6413-0179 (Hsin-Yi Lai)

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