Aquaporin-Targeted Therapeutics: State-of-the-Field

Tradtrantip, Lukmanee; Jin, Bjung-Ju; Yao, Xiaoming; Anderson, Marc O.; Verkman, A. S.

doi:10.1007/978-94-024-1057-0_16

Cited by 62 publications

(67 citation statements)

References 48 publications

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“…Therefore, a s t r o c y t i c A Q P -4 s e e m s t o r e p r e s e n t a p o s s i b l e pharmacological candidate to be targeted in AD at its earliest stage, before abnormal protein accumulation and neurodegeneration occur. So far, some molecules have been tested for activity to AQP-4, but none in in vitro or in vivo models of AD (Lan et al, 2016;Tradtrantip et al, 2017). Some phytocompounds with antioxidant properties have shown to be active on AQP-4.…”

Section: Pharmacological Tools Targeting Aqp-4mentioning

confidence: 99%

Altered Waste Disposal System in Aging and Alzheimer’s Disease: Focus on Astrocytic Aquaporin-4

et al. 2020

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Among the diverse cell types included in the general population named glia, astrocytes emerge as being the focus of a growing body of research aimed at characterizing their heterogeneous and complex functions. Alterations of both their morphology and activities have been linked to a variety of neurological diseases. One crucial physiological need satisfied by astrocytes is the cleansing of the cerebral tissue from waste molecules. Several data demonstrate that aquaporin-4 (AQP-4), a protein expressed by astrocytes, is crucially important for facilitating the removal of waste products from the brain. Aquaporins are water channels found in all district of the human organism and the most abundant isoform in the brain is AQP-4. This protein is involved in a myriad of astrocytic activities, including calcium signal transduction, potassium buffering, synaptic plasticity, astrocyte migration, glial scar formation and neuroinflammation. The highest density of AQP-4 is found at the astrocytic domains closest to blood vessels, the endfeet that envelop brain vessels, with low to zero expression in other astrocytic membrane regions. Increased AQP-4 expression and loss of polarization have recently been documented in altered physiological conditions. Here we review the latest findings related to aging and Alzheimer's disease (AD) on this topic, as well as the available knowledge on pharmacological tools to target AQP-4.

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Section: Pharmacological Tools Targeting Aqp-4mentioning

confidence: 99%

Altered Waste Disposal System in Aging and Alzheimer’s Disease: Focus on Astrocytic Aquaporin-4

et al. 2020

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“…AQP4 expression and activity in various neurological disorders has been examined, and several intriguing discoveries have been made. In cerebral edema and ischemia, AQP4 expression is increased [15,16], and inhibition of AQP4 activity, either by knockout or pretreatment with an inhibitor has been shown to cause a reduction in edema size and formation [7,[17][18][19]. However, in vasogenic edema the loss of AQP4 activity actually aggravates the condition, due to the loss of ability to remove excess water from the brain tissue [2,5,16].…”

Section: Introductionmentioning

confidence: 99%

“…Finally, AQP4 has been shown to have many roles in Alzheimer's disease, including possibly mediating the clearance of amyloid-β [36][37][38][39], and AQP4 deficiency leads to impaired learning and memory via disruption of both the glutamate transport pathway and K + ion homeostasis [40][41][42][43]. With the increase in interest in AQP4 as a potential therapeutic target [1,5,16,19], and the implications AQP4 activity has on many neurological disorders [7,14,[16][17][18][21][22][23]25,[30][31][32][33][34]42,43], it is important to have a clear understanding of the myriad of ways in which AQP4 is known to be regulated.…”

Section: Introductionmentioning

confidence: 99%

Regulation of AQP4 in the Central Nervous System

Vandebroek

Yasui

2020

IJMS

106

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Aquaporin-4 (AQP4) is the main water channel protein expressed in the central nervous system (CNS). AQP4 is densely expressed in astrocyte end-feet, and is an important factor in CNS water and potassium homeostasis. Changes in AQP4 activity and expression have been implicated in several CNS disorders, including (but not limited to) epilepsy, edema, stroke, and glioblastoma. For this reason, many studies have been done to understand the various ways in which AQP4 is regulated endogenously, and could be regulated pharmaceutically. In particular, four regulatory methods have been thoroughly studied; regulation of gene expression via microRNAs, regulation of AQP4 channel gating/trafficking via phosphorylation, regulation of water permeability using heavy metal ions, and regulation of water permeability using small molecule inhibitors. A major challenge when studying AQP4 regulation is inter-method variability. A compound or phosphorylation which shows an inhibitory effect in vitro may show no effect in a different in vitro method, or even show an increase in AQP4 expression in vivo. Although a large amount of variability exists between in vitro methods, some microRNAs, heavy metal ions, and two small molecule inhibitors, acetazolamide and TGN-020, have shown promise in the field of AQP4 regulation.

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“…Vol. 25, N2, 2019 стимуляцию регуляторных белков системы комплемента, таких как CD59-ингибитор мембраноатакующего комплекса [3,107].…”

Section: аквапоринunclassified

Cerebrospinal fluid flow. Part 2. Aquaporins and their role in CNS water homeostasis

2019

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The discovery and further investigation of functional characteristics of specialized water channels-aquaporins was one of the milestones in the study of the mechanisms for maintaining water homeostasis of CNS. The present review deals with base ideas concerning the role of aquaporins in the processes of water transport, such as regulating cell volume, controlling the size of extracellular space, production and drainage of cerebrospinal fluid. Certain pathological conditions caused by a violation of water homeostasis and the drainage system of the central nervous system are considered.

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Aquaporin-Targeted Therapeutics: State-of-the-Field

Cited by 62 publications

References 48 publications

Altered Waste Disposal System in Aging and Alzheimer’s Disease: Focus on Astrocytic Aquaporin-4

Altered Waste Disposal System in Aging and Alzheimer’s Disease: Focus on Astrocytic Aquaporin-4

Regulation of AQP4 in the Central Nervous System

Cerebrospinal fluid flow. Part 2. Aquaporins and their role in CNS water homeostasis

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