Multifaceted Roles of Aquaporins in the Pathogenesis of Alzheimer’s Disease

Yamada, Kaoru

doi:10.3390/ijms24076528

Cited by 11 publications

(4 citation statements)

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“…The glymphatic system can be influenced by various physiological factors, including sleep [ 2 ], circadian rhythm [ 67 ], and anesthetic agents [ 68 ], and the fixation method of the brain is known to influence the structure of perivascular spaces critical for the glymphatic system [ 4 ]. Furthermore, the majority of the studies highly depend on AQP4-deficient mice as genetic models to study glymphatic system, but it’s important to consider that AQP4 may have other physiological functions beyond the glymphatic system [ 69 ].…”

Section: Future Directionsmentioning

confidence: 99%

Involvement of the glymphatic/meningeal lymphatic system in Alzheimer’s disease: insights into proteostasis and future directions

Yamada,

Iwatsubo

2024

Cell. Mol. Life Sci.

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Background Alzheimer’s disease (AD) is pathologically characterized by the abnormal accumulation of Aβ and tau proteins. There has long been a keen interest among researchers in understanding how Aβ and tau are ultimately cleared in the brain. The discovery of this glymphatic system introduced a novel perspective on protein clearance and it gained recognition as one of the major brain clearance pathways for clearing these pathogenic proteins in AD. This finding has sparked interest in exploring the potential contribution of the glymphatic/meningeal lymphatic system in AD. Furthermore, there is a growing emphasis and discussion regarding the possibility that activating the glymphatic/meningeal lymphatic system could serve as a novel therapeutic strategy against AD. Objectives Given this current research trend, the primary focus of this comprehensive review is to highlight the role of the glymphatic/meningeal lymphatic system in the pathogenesis of AD. The discussion will encompass future research directions and prospects for treatment in relation to the glymphatic/meningeal lymphatic system.

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Section: Future Directionsmentioning

confidence: 99%

Involvement of the glymphatic/meningeal lymphatic system in Alzheimer’s disease: insights into proteostasis and future directions

Yamada,

Iwatsubo

2024

Cell. Mol. Life Sci.

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“…Neurodegenerative diseases impact millions globally, constituting a diverse set of disorders that specifically target certain regions of the Central Nervous System (CNS). These diseases typically result in a sustained decline in cognitive or motor functions, contingent upon the distinct type of neuronal cells undergoing selective degeneration [ 103 ]. Predominantly, these pathological states are correlated with aging.…”

Section: Implications Of Aquaporins In Degenerative and Acute Brain P...mentioning

confidence: 99%

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

Toader,

Tataru,

Florian

et al. 2023

IJMS

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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.

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“…The glymphatic system plays a critical role in the clearance of protein depositing in the interstitial space of the brain, and AQP4 has been established as a central element for fluid transit between perivascular spaces that allow for an adequate transit of liquid and substances to the exit pathways of the brain. As detailed in the review by Yamada, C. [ 2 ], the crucial roles of AQP4 in Alzheimer’s disease pathogenesis are strongly supported by experiments conducted in animal models lacking AQP4, in which a clear exacerbation of the pathology of AD was observed. Furthermore, most studies indicate that glymphatic clearance is suppressed in AD patients, but the exact mechanisms by which the regulation of AQP4 expression contributes to suppression of the glymphatic system require further exploration.…”

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confidence: 95%