Lapshina Ksenia V, Ekimova Irina V
Laboratory of Comparative Thermophysiology, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, Russia.
Int J Mol Sci. 2024 Jan 30;25(3):1672. doi: 10.3390/ijms25031672.
The water-selective channel aquaporin-4 (AQP4) is implicated in water homeostasis and the functioning of the glymphatic system, which eliminates various metabolites from the brain tissue, including amyloidogenic proteins. Misfolding of the α-synuclein protein and its post-translational modifications play a crucial role in the development of Parkinson's disease (PD) and other synucleopathies, leading to the formation of cytotoxic oligomers and aggregates that cause neurodegeneration. Human and animal studies have shown an interconnection between AQP4 dysfunction and α-synuclein accumulation; however, the specific role of AQP4 in these mechanisms remains unclear. This review summarizes the current knowledge on the role of AQP4 dysfunction in the progression of α-synuclein pathology, considering the possible effects of AQP4 dysregulation on brain molecular mechanisms that can impact α-synuclein modification, accumulation and aggregation. It also highlights future directions that can help study the role of AQP4 in the functioning of the protective mechanisms of the brain during the development of PD and other neurodegenerative diseases.
水选择性通道水通道蛋白4（AQP4）与水稳态以及类淋巴系统的功能有关，该系统可清除脑组织中的各种代谢产物，包括淀粉样蛋白。α-突触核蛋白的错误折叠及其翻译后修饰在帕金森病（PD）和其他突触核蛋白病的发展中起关键作用，导致细胞毒性寡聚体和聚集体的形成，进而引起神经退行性变。人类和动物研究表明AQP4功能障碍与α-突触核蛋白积累之间存在关联；然而，AQP4在这些机制中的具体作用仍不清楚。本综述总结了目前关于AQP4功能障碍在α-突触核蛋白病理学进展中作用的知识，考虑了AQP4失调对可能影响α-突触核蛋白修饰、积累和聚集的脑分子机制的潜在影响。它还强调了未来的研究方向，这些方向有助于研究AQP4在PD和其他神经退行性疾病发展过程中脑保护机制功能中的作用。
