The Laminin-Induced Phosphorylation of PKCδ Regulates AQP4 Distribution and Water Permeability in Rat Astrocytes

Noël, Geoffroy; Tham, Daniel Kai Long; Guadagno, Éric; MacVicar, Brian A.; Moukhles, Hakima

doi:10.1007/s10571-020-00944-w

Cited by 9 publications

(4 citation statements)

References 91 publications

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“…Studies indicate a significant role for multiple BM proteins, including laminin isoforms 111 and 211, as well as agrin and astrocytic β 1− integrin in maintaining AQP4 polarization (Noell et al, 2009;Robel et al, 2009;Fallier-Becker et al, 2011;Menezes et al, 2014;Yao et al, 2014;Gautam et al, 2016;Noël et al, 2019Noël et al, , 2020. Laminins have been shown to promote AQP4 polarization via binding to the dystroglycan associated complex on the cell membrane (Noël et al, 2020), which has been shown to bind AQP4 via α-syntrophin and locally modulate its expression on astrocytic endfeet (Noell et al, 2011;Tham et al, 2016). Interestingly, this process may be disrupted in CAA, as recent transcriptional network analysis of human astrocytic endfoot genes showed reduced levels of dystroglycan, dystrobrevin, and α-syntrophin in AD patients (Simon et al, 2018).…”

Section: Bm Remodeling May Impair Perivascular Aqp4 Polarizationmentioning

confidence: 99%

The Role of Basement Membranes in Cerebral Amyloid Angiopathy

2020

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Dementia is a neuropsychiatric syndrome characterized by cognitive decline in multiple domains, often leading to functional impairment in activities of daily living, disability, and death. The most common causes of age-related progressive dementia include Alzheimer’s disease (AD) and vascular cognitive impairment (VCI), however, mixed disease pathologies commonly occur, as epitomized by a type of small vessel pathology called cerebral amyloid angiopathy (CAA). In CAA patients, the small vessels of the brain become hardened and vulnerable to rupture, leading to impaired neurovascular coupling, multiple microhemorrhage, microinfarction, neurological emergencies, and cognitive decline across multiple functional domains. While the pathogenesis of CAA is not well understood, it has long been thought to be initiated in thickened basement membrane (BM) segments, which contain abnormal protein deposits and amyloid-β (Aβ). Recent advances in our understanding of CAA pathogenesis link BM remodeling to functional impairment of perivascular transport pathways that are key to removing Aβ from the brain. Dysregulation of this process may drive CAA pathogenesis and provides an important link between vascular risk factors and disease phenotype. The present review summarizes how the structure and composition of the BM allows for perivascular transport pathways to operate in the healthy brain, and then outlines multiple mechanisms by which specific dementia risk factors may promote dysfunction of perivascular transport pathways and increase Aβ deposition during CAA pathogenesis. A better understanding of how BM remodeling alters perivascular transport could lead to novel diagnostic and therapeutic strategies for CAA patients.

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Section: Bm Remodeling May Impair Perivascular Aqp4 Polarizationmentioning

confidence: 99%

The Role of Basement Membranes in Cerebral Amyloid Angiopathy

2020

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“…The anchoring mechanism has been revealed and reviewed elsewhere (Nagelhus & Ottersen, 2013; Törnroth‐Horsefield et al, 2022). It is known that the anchoring of the AQP4 protein is dependent on several ECM proteins, for example, laminin and dystroglycan, in rodent astrocytes (Noel et al, 2021; Sato et al, 2018). In particular, pericytes secrete laminin and with that they contribute to maintaining the integrity of the BBB (Gautam et al, 2016).…”

Section: Does Ahr Signalling Disturb Glymphatic Regulation In Ad?mentioning

confidence: 99%

Aryl hydrocarbon receptor impairs circadian regulation in Alzheimer's disease: Potential impact on glymphatic system dysfunction

Salminen

2024

Eur J of Neuroscience

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Circadian clocks maintain diurnal rhythms of sleep–wake cycle of 24 h that regulate not only the metabolism of an organism but also many other periodical processes. There is substantial evidence that circadian regulation is impaired in Alzheimer's disease. Circadian clocks regulate many properties known to be disturbed in Alzheimer's patients, such as the integrity of the blood–brain barrier (BBB) as well as the diurnal glymphatic flow that controls waste clearance from the brain. Interestingly, an evolutionarily conserved transcription factor, that is, aryl hydrocarbon receptor (AhR), impairs the function of the core clock proteins and thus could disturb diurnal rhythmicity in the BBB. There is abundant evidence that the activation of AhR signalling inhibits the expression of the major core clock proteins, such as the brain and muscle arnt‐like 1 (BMAL1), clock circadian regulator (CLOCK) and period circadian regulator 1 (PER1) in different experimental models. The expression of AhR is robustly increased in the brains of Alzheimer's patients, and protein level is enriched in astrocytes of the BBB. It seems that AhR signalling inhibits glymphatic flow since it is known that (i) activation of AhR impairs the function of the BBB, which is cooperatively interconnected with the glymphatic system in the brain, and (ii) neuroinflammation and dysbiosis of gut microbiota generate potent activators of AhR, which are able to impair glymphatic flow. I will examine current evidence indicating that activation of AhR signalling could disturb circadian functions of the BBB and impair glymphatic flow and thus be involved in the development of Alzheimer's pathology.

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“…Data provided by antibody microarray assay services such as those offered by Kinexus Bioinformatics and Full Moon Biosystems can be directly uploaded. Both companies’ microarrays have recently been used to quantify protein expression and covalent modification, such as in studies of the central nervous system [10], cancer [11], and infectious diseases [12]. Data provided by similar microarray services must be converted to the general user data format, described next.…”

Section: General Descriptionmentioning

confidence: 99%

CAT PETR: A Graphical User Interface for Differential Analysis of Phosphorylation and Expression Data

Flanagan

Av‐Gay

Pelech

et al. 2023

Preprint

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Analysis of signal transduction pathways relies on monitoring global changes in cellular response to perturbation or genetic manipulation. Antibody microarray data provides an increasingly viable tool for the monitoring and analyzing high throughput expression and phosphorylation data. However, computational tools designed specifically for the analysis of antibody microarray data are few and far between; forcing researchers to use applications primarily designed for other data types. Here we present CAT PETR (Convenient Analysis Tool for Phosphorylation and Expression Testing), a user friendly web application that provides interactive and publication ready plots for the differential analysis of expression and phosphorylation data collected via antibody microarrays. Our tool is made available as a web application at https://av-gay-ubc.shinyapps.io/CAT-PETR/. The code is publicly available on GitHub (https://github.com/Raif-fl/CAT-PETR) with documentation containing tutorials and datasets.

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The Laminin-Induced Phosphorylation of PKCδ Regulates AQP4 Distribution and Water Permeability in Rat Astrocytes

Cited by 9 publications

References 91 publications

The Role of Basement Membranes in Cerebral Amyloid Angiopathy

The Role of Basement Membranes in Cerebral Amyloid Angiopathy

Aryl hydrocarbon receptor impairs circadian regulation in Alzheimer's disease: Potential impact on glymphatic system dysfunction

CAT PETR: A Graphical User Interface for Differential Analysis of Phosphorylation and Expression Data

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