Aquaporin-4 mediates astrocyte response to β-amyloid

Yang, Wei; Wu, Qi; Chan, Yuan; Gao, Junying; Xiao, Ming; Gu, Minxia; Ding, Jiong; Hu, Gang

doi:10.1016/j.mcn.2012.02.002

Cited by 77 publications

(65 citation statements)

References 60 publications

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“…It had two pathways that intervened in stroke-mediated cerebral edema, including the inhibition of AQP4 channels and acid-sensing ion channels (ASICs). The present results revealed that the absence of AQP4 decreased Ab-induced reactive morphological changes and GFAP up-regulation of astrocytes [63], indicating that AQP4 is involved in astrocyte activation and Ab clearing. Moreover, Yang et al [63] found that AQP4 deficiency decreased Ab uptake and, in turn, attenuated changes in MAPK signaling pathways and reduced astrocyte activity and apoptosis.…”

Section: Non-steroidal Anti-inflammatory Drugs and Aqp4-related Neurosupporting

confidence: 55%

A research update on the potential roles of aquaporin 4 in neuroinflammation

et al. 2015

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The presence of aquaporins (AQPs) in the brain has led to intense research on the underlying roles of this family of proteins under both normal and pathological conditions. Aquaporin 4 (AQP4) is the major water-channel membrane protein expressed in the central nervous system (CNS), primarily in astrocytes. Emerging evidence suggests that AQP4 could play an important role in water and ion homeostasis in the brain, and it has been studied in various brain pathological conditions. However, far less is known about the potential for AQP4 to influence neuroinflammation and, furthermore, its potential role in neurodegenerative disorders such as Alzheimer's disease (AD). It has been suggested that the pathogenesis of many clinical diseases, such as neuromyelitis optica (NMO), multiple sclerosis (MS) and brain injuries, is related to the regulation of AQP4 expression. Investigating the effects of AQP4 on microglia and astrocytes could be important to understand its role in the pathogenesis of neuroinflammation. Although the exact roles of non-steroidal anti-inflammatory drugs (NSAIDs) in protection against the detrimental effects of neuroinflammation remain unclear, research into the possible neuroprotective effects of AQP4 against neuroinflammation regulation seems to be important for future investigations.

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Section: Non-steroidal Anti-inflammatory Drugs and Aqp4-related Neurosupporting

confidence: 55%

A research update on the potential roles of aquaporin 4 in neuroinflammation

et al. 2015

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“…126,127 In a recent study, it was shown that astrocytes upregulate AQP4 expression in response to lower concentrations of Ab42, whereas exposure to higher concentrations results in downregulation of AQP4. 128 Knockout of AQP4 (ref. 121) and reduction of AQP4 by endothelial-specific agrin knockout 129 result in Ab accumulation in the brain with no apparent signs of BBB disruption.…”

Section: Cerebrospinal Fluid/interstitial Fluid Bulk Flow Brain Barrmentioning

confidence: 99%

“…121,129 However, AQP4 knockout in astrocytes protects against Ab-induced activation and toxicity. 128 Therefore, variable changes in AQP4 may reflect a varying necessity for promoting Ab clearance versus protecting against gliosis as Ab concentrations rise to pathologic levels. In contrast to AQP4, aquaporin 1 (AQP1) localization in the CNS is primarily at CP epithelial cells under physiologic conditions and plays an important role in CSF dynamics.…”

Section: Cerebrospinal Fluid/interstitial Fluid Bulk Flow Brain Barrmentioning

confidence: 99%

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

Erickson

Banks

2013

J Cereb Blood Flow Metab

458

363

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The blood-brain barrier (BBB) plays critical roles in the maintenance of central nervous system (CNS) homeostasis. Dysfunction of the BBB occurs in a number of CNS diseases, including Alzheimer's disease (AD). A prevailing hypothesis in the AD field is the amyloid cascade hypothesis that states that amyloid-b (Ab) deposition in the CNS initiates a cascade of molecular events that cause neurodegeneration, leading to AD onset and progression. In this review, the participation of the BBB in the amyloid cascade and in other mechanisms of AD neurodegeneration will be discussed. We will specifically focus on three aspects of BBB dysfunction: disruption, perturbation of transporters, and secretion of neurotoxic substances by the BBB. We will also discuss the interaction of the BBB with components of the neurovascular unit in relation to AD and the potential contribution of AD risk factors to aspects of BBB dysfunction. From the results discussed herein, we conclude that BBB dysfunction contributes to AD through a number of mechanisms that could be initiated in the presence or absence of Ab pathology. Keywords: Alzheimer's disease; blood-brain barrier; cerebrospinal fluid; diabetes; inflammation; neurovascular unit INTRODUCTION Alzheimer's disease (AD) is the most common type of dementia, and affects B36 million individuals worldwide (http://www.alz. co.uk/research/world-report). The majority of individuals afflicted with AD initially present with symptoms of memory loss and cognitive impairment late in life (Z65 years old). These symptoms increase in severity as AD progresses, often become so debilitating that institutionalization is necessary, and are eventually fatal. Therefore, AD is a disease with tremendous socioeconomic cost. Because of the growing aged population and lack of treatments that can prevent or slow disease progression, future AD prevalence is expected to increase to an extent that it may threaten the sustainability of healthcare systems worldwide. This necessitates a global effort to better understand AD, with the goal of developing treatments that can prevent or slow AD progression. Journal of Cerebral BloodMuch of the focus in AD research has been on amyloid-b peptide (Ab) and tau, which are the protein constituents of the hallmark senile plaques and neurofibrillary tangles that pathologically define AD. The amyloid cascade hypothesis, initially proposed by Hardy and Higgins in 1992, 1 updated by Hardy and Selkoe in 2002, 2 and still a prevalent focus of AD research today, states that deposition of Ab in the brain is the initiating event in AD. Although the hypothesis remains generally accepted, it is also increasingly evident that Ab plays a complex, multifaceted role in AD progression. In rare, familial forms of AD, mutations in the Ab precursor protein (APP) or in presenilin proteins, the enzymes that cleave Ab from APP, cause increased Ab deposition. In the remainder of AD cases, it is thought that Ab deposition results from deficient clearance. 2 Multiple routes of clearance have been elucidat...

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“…This contradiction can possibly be explained by a study showing upregulation of AQP4 in the neuropil surrounding plaques and loss of AQP4 from endfoot membranes at sites of perivascular amyloid deposits (346), indicating a redistribution of AQP4 from endfoot membranes to non-endoot domains. Furthermore, low concentration of amyloid-β induced AQP4-expression in astrocytic cell cultures, whereas higher concentrations reduced the expression (347). Finally, deletion of AQP4 decrease amyloid-β induced gliosis in astrocytic cultures, indicating that AQP4 is involved in astrocyte activation following amyloid-β exposure (347).…”

Section: Aqp4 and Chronic Neurodegenerative Diseasesmentioning

confidence: 97%

“…Furthermore, low concentration of amyloid-β induced AQP4-expression in astrocytic cell cultures, whereas higher concentrations reduced the expression (347). Finally, deletion of AQP4 decrease amyloid-β induced gliosis in astrocytic cultures, indicating that AQP4 is involved in astrocyte activation following amyloid-β exposure (347). Another link between AQP4 and AD has been proposed through the glymphatic system, in which Aqp4 -/-mice exhibited delayed clearance of intraparenchymally injected amyloid-β (320).…”

Section: Aqp4 and Chronic Neurodegenerative Diseasesmentioning

confidence: 99%