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      MicroRNAs in oligodendrocyte development and remyelination

      1 , 2 , 1 , 3 , 4 , 5
      Journal of Neurochemistry
      Wiley

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          Abstract

          <p class="first" id="d2482515e99">Oligodendrocytes are the glial cells responsible for the formation of myelin around axons of the central nervous system (CNS). Myelin is an insulating layer that allows electrical impulses to transmit quickly and efficiently along neurons. If myelin is damaged, as in chronic demyelinating disorders such as multiple sclerosis (MS), these impulses slow down. Remyelination by oligodendrocytes is often ineffective in MS, in part because of the failure of oligodendrocyte precursor cells (OPCs) to differentiate into mature, myelinating oligodendrocytes. The process of oligodendrocyte differentiation is tightly controlled by several regulatory networks involving transcription factors, intracellular signaling pathways, and extrinsic cues. Understanding the factors that regulate oligodendrocyte development is essential for the discovery of new therapeutic strategies capable of enhancing remyelination. Over the past decade, microRNAs (miRNAs) have emerged as key regulators of oligodendrocyte development, exerting effects on cell specification, proliferation, differentiation, and myelination. This article will review the role of miRNAs on oligodendrocyte biology and discuss their potential as promising therapeutic tools for remyelination. </p>

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          MicroRNAs: target recognition and regulatory functions.

          MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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            A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination

            Summary MicroRNAs are important players in stem cell biology. Among them, microRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain. Whether miR-9 plays a role in neural stem cell self-renewal and differentiation is unknown. We showed previously that nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector lacking the miR-9 recognition site rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses miR-9 pri-miRNA expression. MiR-9, by forming a negative regulatory loop with TLX, establishes a model for controlling the balance between neural stem cell proliferation and differentiation.
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              Is Open Access

              Targeting and Crossing the Blood-Brain Barrier with Extracellular Vesicles

              The blood–brain barrier (BBB) is one of the most complex and selective barriers in the human organism. Its role is to protect the brain and preserve the homeostasis of the central nervous system (CNS). The central elements of this physical and physiological barrier are the endothelial cells that form a monolayer of tightly joined cells covering the brain capillaries. However, as endothelial cells regulate nutrient delivery and waste product elimination, they are very sensitive to signals sent by surrounding cells and their environment. Indeed, the neuro-vascular unit (NVU) that corresponds to the assembly of extracellular matrix, pericytes, astrocytes, oligodendrocytes, microglia and neurons have the ability to influence BBB physiology. Extracellular vesicles (EVs) play a central role in terms of communication between cells. The NVU is no exception, as each cell can produce EVs that could help in the communication between cells in short or long distances. Studies have shown that EVs are able to cross the BBB from the brain to the bloodstream as well as from the blood to the CNS. Furthermore, peripheral EVs can interact with the BBB leading to changes in the barrier’s properties. This review focuses on current knowledge and potential applications regarding EVs associated with the BBB.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Journal of Neurochemistry
                Journal of Neurochemistry
                Wiley
                0022-3042
                1471-4159
                August 2022
                May 10 2022
                August 2022
                : 162
                : 4
                : 310-321
                Affiliations
                [1 ]Regenerative Medicine Program Ottawa Hospital Research Institute Ottawa Ontario Canada
                [2 ]Program in Biomedical Sciences, Faculty of Science University of Ottawa Ottawa Ontario Canada
                [3 ]Department of Cellular and Molecular Medicine University of Ottawa Ottawa Ontario Canada
                [4 ]Centre for Neuromuscular Disease University of Ottawa Ottawa Ontario Canada
                [5 ]Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, and Department of Medicine University of Ottawa Ottawa Ontario Canada
                Article
                10.1111/jnc.15618
                35536759
                6a7b7c66-a11a-45dc-82d0-5a4687624df9
                © 2022

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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