中山大学学报（医学科学版）2026，Vol.47Issue(3)：440-450,11.DOI:10.11714/jsysu.med.YX20250178
水通道蛋白4介导的类淋巴功能障碍与帕金森病
Aquaporin-4 Mediated Glymphatic Dysfunction and Parkinson's Disease
摘要
Abstract
Parkinson's disease(PD)is a central neurodegenerative disorder with insidious onset and slow progression.It is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the abnormal aggregation of α-synuclein(α-Syn),resulting in the formation of Lewy bodies.These pathological changes give rise to motor dysfunction,sleep disturbances,cognitive impairment,and other symptoms,thereby markedly reducing patients'quality of life.Current treatments remain largely symptomatic,including dopaminergic replacement therapy and deep brain stimulation(DBS),while long-term adverse effects and declining efficacy in advanced stages remain unresolved.Therefore,the development of disease-modifying therapies capable of delaying or reversing disease progression is of critical importance.Aquaporin-4(AQP4)is the most abundant water channel in the brain and is predominantly expressed in astrocytic endfeet,where it plays a key role in maintaining cerebral water homeostasis,blood-brain barrier integrity,and glymphatic waste clearance.Recent studies have demonstrated that both the expression level and polarization of AQP4 are altered in PD animal models and in brain tissues from patients with PD,and these alterations are closely associated with glymphatic dysfunction,impaired α-Syn clearance,disruption of central nervous system homeostasis,and activation of neuroinflammation.Following the cascade of"AQP4 alteration-impaired glymphatic clearance-α-Syn deposition-neuroinflammation-PD progression",this review outlines the basis of AQP4 polarization and glymphatic function,summarizes the potential mechanisms by which AQP4 abnormalities promote α-Syn accumulation and inflammatory amplification,and synthesizes current clinical evidence and therapeutic advances.Nevertheless,inconsistencies across experimental models and PD subtypes remain,and the causal role of AQP4 as well as population heterogeneity has yet to be fully elucidated.Future large-scale,long-term,subtype-stratified studies are warranted to explore precise regulatory strategies targeting AQP4 and to validate its safety and efficacy as a novel disease-modifying therapeutic target for PD.关键词
帕金森病/水通道蛋白4/α-突触核蛋白/类淋巴系统/神经炎症/疾病修饰治疗Key words
Parkinson's disease/aquaporin-4/α-Synuclein/glymphatic system/neuroinflammation/disease-modifying therapy分类
医药卫生引用本文复制引用
魏圣楠,任彬彬..水通道蛋白4介导的类淋巴功能障碍与帕金森病[J].中山大学学报（医学科学版）,2026,47(3):440-450,11.基金项目
河南省中医药传承与创新人才工程(仲景工程)中医药学科拔尖人才(CZ0262-10-02) （仲景工程）
河南省中医药科学研究传承创新中心专项课题(HY-B0366-42) （HY-B0366-42）
