From Homeostasis to Pathology: Decoding the Multifaceted Impact of Aquaporins in the Central Nervous System

Aquaporins (AQPs), integral membrane proteins facilitating selective water and solute transport across cell membranes, have been the focus of extensive research over the past few decades. Particularly noteworthy is their role in maintaining cellular homeostasis and fluid balance in neural compartments, as dysregulated AQP expression is implicated in various degenerative and acute brain pathologies. This article provides an exhaustive review on the evolutionary history, molecular classification, and physiological relevance of aquaporins, emphasizing their significance in the central nervous system (CNS). The paper journeys through the early studies of water transport to the groundbreaking discovery of Aquaporin 1, charting the molecular intricacies that make AQPs unique. It delves into AQP distribution in mammalian systems, detailing their selective permeability through permeability assays. The article provides an in-depth exploration of AQP4 and AQP1 in the brain, examining their contribution to fluid homeostasis. Furthermore, it elucidates the interplay between AQPs and the glymphatic system, a critical framework for waste clearance and fluid balance in the brain. The dysregulation of AQP-mediated processes in this system hints at a strong association with neurodegenerative disorders such as Parkinson’s Disease, idiopathic normal pressure hydrocephalus, and Alzheimer’s Disease. This relationship is further explored in the context of acute cerebral events such as stroke and autoimmune conditions such as neuromyelitis optica (NMO). Moreover, the article scrutinizes AQPs at the intersection of oncology and neurology, exploring their role in tumorigenesis, cell migration, invasiveness, and angiogenesis. Lastly, the article outlines emerging aquaporin-targeted therapies, offering a glimpse into future directions in combatting CNS malignancies and neurodegenerative diseases.