Endothelial Unc5B controls blood-brain barrier integrity

Boyé, Kevin; Geraldo, Luiz Henrique Medeiros; Furtado, Jessica; Pibouin-Fragner, Laurence; Poulet, Mathilde; D, Kim; Nelson, Bryce; Xu, Ya; Jacob, Laurent; Maïssa, Nawal; Tavitian, Bertrand; Agalliu, Dritan; Claesson‐Welsh, Lena; Sl, Ackerman; Eichmann, Anne

doi:10.1101/2021.05.06.442974

Cited by 5 publications

(6 citation statements)

References 47 publications

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“…Canonical Wnt signaling-associated genes Tle3, Tcf7l1, Tcf7, Axin1, and Axin2 were upregulated and Wnt signaling has well established roles in kidney development . Recently, it was shown that netrin-1 enhances the interaction of Unc5b with LRP6, a Wnt co-receptor, thereby activating Wnt/-catenin signaling and linking the two signaling pathways in blood-brain barrier integrity (Boyé et al, 2022). However, with Wnt pathway genes upregulated in the absence of netrin-1, this cooperative signaling may not be active in kidney endothelium.…”

Section: Development • Accepted Manuscriptmentioning

confidence: 99%

Netrin 1 directs vascular patterning and maturity in the developing kidney

Honeycutt,

N'Guetta,

Hardesty

et al. 2023

Development

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The kidneys intricate vascular system supports body fluid and organ homeostasis. However, little is known about how vascular architecture is established during kidney development. More specifically, how signals from the kidney influence vessel maturity and patterning remains poorly understood. Netrin-1 (Ntn1) is a secreted ligand critical for vessel and neuronal guidance. Here, we demonstrate that Ntn1 is expressed by Foxd1+ stromal progenitors in the developing kidney and conditional deletion (Foxd1GC/+;Ntn1fl/fl) results in hypoplastic kidneys with extended nephrogenesis. Wholemount 3D analyses additionally revealed the loss of a predictable vascular pattern in Foxd1GC/+;Ntn1fl/fl kidneys. As vascular patterning has been linked to vessel maturity, we investigated arterialization. Quantification of the CD31+ endothelium at E15.5 revealed no differences in metrics such as the number of branches or branch points, whereas the arterial vascular smooth muscle metrics were significantly reduced at both E15.5 and P0. In support of our observed phenotypes, whole kidney RNA-seq revealed disruptions to genes and programs associated with stromal cells, vasculature, and differentiating nephrons. Together, our findings highlight the significance of netrin-1 to proper vascularization and kidney development.

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Section: Development • Accepted Manuscriptmentioning

confidence: 99%

Netrin 1 directs vascular patterning and maturity in the developing kidney

Honeycutt,

N'Guetta,

Hardesty

et al. 2023

Development

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“…Different strategies have been employed to improve the BBB penetration proficiency of NPs. Among various approaches, 145−148 a common way is to regulate the Wnt/βcatenin signaling produced by glial cells and reduce their binding to multiprotein receptor complexes on brain ECs 23 for cargo administration with high BBB penetration potential. The main limitation of all these methods, however, could be the structural damage and, hence, the dysfunction of the BBB.…”

Section: Properties Affecting Nanoparticle Crossing Through the Bbbmentioning

confidence: 99%

“…22 Furthermore, the endothelial Wnt/β-catenin pathway has been found to be one of the major molecular drivers of barriergenesis in the brain. 23,24 Hussain et al 25 demonstrated the importance of β-catenin in maintaining BBB integrity using endothelial-specific β-catenin conditional knockout mice. These mice exhibited severe leakage of plasma proteins IgG and albumin into the cerebral cortex.…”

Section: Astrocytesmentioning

confidence: 99%

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Zha,

Liu,

et al. 2024

ACS Nano

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The blood−brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.

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“…19,20 The entry of suprangiolar vascular endothelial cells into the CNS is accompanied by activation of the Wnt/β-catenin pathway at specific times during the embryonic period. 21 Angiogenesis is a natural defense mechanism that helps restore oxygen and nutrient supply to the affected brain tissue after an IS. Wnt7a/7b participates in angiogenesis in the CNS by activating the Wnt/β-catenin pathway.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Natural Compounds from Herbs and Nutraceuticals in Alleviating Neurological Disorders: Targeting the Wnt Signaling Pathway

Li,

Wang,

Zhang

2024

J. Agric. Food Chem.

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As an important signaling pathway in multicellular eukaryotes, the Wnt signaling pathway participates in a variety of physiological processes. Recent studies have confirmed that the Wnt signaling pathway plays an important role in neurological disorders such as stroke, Alzheimer's disease, and Parkinson's disease. The regulation of Wnt signaling by natural compounds in herbal medicines and nutraceuticals has emerged as a potential strategy for the development of new drugs for neurological disorders. Purpose: The aim of this review is to evaluate the latest research results on the efficacy of natural compounds derived from herbs and nutraceuticals in the prevention and treatment of neurological disorders by regulating the Wnt pathway in vivo and in vitro. A manual and electronic search was performed for English articles available from PubMed, Web of Science, and ScienceDirect from the January 2010 to February 2023. Keywords used for the search engines were "natural products,″ "plant derived products,″ "Wnt+ clinical trials,″ and "Wnt+,″ and/or paired with "natural products″/″plant derived products", and "neurological disorders." A total of 22 articles were enrolled in this review, and a variety of natural compounds from herbal medicine and nutritional foods have been shown to exert therapeutic effects on neurological disorders through the Wnt pathway, including curcumin, resveratrol, and querctrin, etc. These natural products possess antioxidant, anti-inflammatory, and angiogenic properties, confer neurovascular unit and blood−brain barrier integrity protection, and affect neural stem cell differentiation, synaptic formation, and neurogenesis, to play a therapeutic role in neurological disorders. In various in vivo and in vitro studies and clinical trials, these natural compounds have been shown to be safe and tolerable with few adverse effects. Natural compounds may serve a therapeutic role in neurological disorders by regulating the Wnt pathway. This summary of the research progress of natural compounds targeting the Wnt pathway may provide new insights for the treatment of neurological disorders and potential targets for the development of new drugs.

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Endothelial Unc5B controls blood-brain barrier integrity

Cited by 5 publications

References 47 publications

Netrin 1 directs vascular patterning and maturity in the developing kidney

Netrin 1 directs vascular patterning and maturity in the developing kidney

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Therapeutic Potential of Natural Compounds from Herbs and Nutraceuticals in Alleviating Neurological Disorders: Targeting the Wnt Signaling Pathway

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