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      Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS

      review-article
      * , *
      International Journal of Molecular Sciences
      MDPI
      cerebrospinal fluid, choroid plexus, secretion

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          Abstract

          Cerebrospinal fluid (CSF) is the liquid that fills the brain ventricles. CSF represents not only a mechanical brain protection but also a rich source of signalling factors modulating diverse processes during brain development and adulthood. The choroid plexus (CP) is a major source of CSF and as such it has recently emerged as an important mediator of extracellular signalling within the brain. Growing interest in the CP revealed its capacity to release a broad variety of bioactive molecules that, via CSF, regulate processes across the whole central nervous system (CNS). Moreover, CP has been also recognized as a sensor, responding to altered composition of CSF associated with changes in the patterns of CNS activity. In this review, we summarize the recent advances in our understanding of the CP as a signalling centre that mediates long-range communication in the CNS. By providing a detailed account of the CP secretory repertoire, we describe how the CP contributes to the regulation of the extracellular environment—in the context of both the embryonal as well as the adult CNS. We highlight the role of the CP as an important regulator of CNS function that acts via CSF-mediated signalling. Further studies of CP–CSF signalling hold the potential to provide key insights into the biology of the CNS, with implications for better understanding and treatment of neuropathological conditions.

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          Most cited references167

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          A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

          Highlights • Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. • This is the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance. • The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. • This case warns the physicians of patients who have CNS symptoms.
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            Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus ‐2 (SARS‐CoV‐2)

            Abstract Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying CNS involvement by SARS‐CoV‐2. This article is protected by copyright. All rights reserved.
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              TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia.

              Genetic variants of TREM2, a protein expressed selectively by microglia in the brain, are associated with Alzheimer's disease (AD). Starting from an unbiased protein microarray screen, we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands of TREM2. Binding of these ligands by TREM2 was abolished or reduced by disease-associated mutations. Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, whereas TREM2 disease variants were impaired in this activity. Trem2 knockout microglia showed reduced internalization of LDL and CLU. β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion. Uptake of Aβ-lipoprotein complexes was reduced in macrophages from human subjects carrying a TREM2 AD variant. These data link three genetic risk factors for AD and reveal a possible mechanism by which mutant TREM2 increases risk of AD. VIDEO ABSTRACT.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                04 July 2020
                July 2020
                : 21
                : 13
                : 4760
                Affiliations
                Department of Experimental Biology, Faculty of Science, Masaryk University, 625 00 Brno, Czech Republic
                Author notes
                Author information
                https://orcid.org/0000-0003-4705-2003
                https://orcid.org/0000-0002-9136-5085
                Article
                ijms-21-04760
                10.3390/ijms21134760
                7369786
                32635478
                fbdcc31d-9a90-4b56-9d0f-8e381ca7c5b1
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 June 2020
                : 02 July 2020
                Categories
                Review

                Molecular biology
                cerebrospinal fluid,choroid plexus,secretion
                Molecular biology
                cerebrospinal fluid, choroid plexus, secretion

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