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http://hdl.handle.net/2445/181715
Title: | Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit |
Author: | Gilbert, Alice Elorza Vidal, Xabier Rancillac, Armelle Chagnot, Audrey Yetim, Mervé Hingot, Vincent Deffieux, Thomas Boulay, Anne Cécile Alvear Perez, Rodrigo Cisternino, Salvatore Martin, Sabrina Taïb, Sonia Gelot, Aontoinette Mignon, Virginie Favier, Maryline Brunet, Isabelle Declèves, Xavier Tanter, Mickael Estévez Povedano, Raúl Vivien, Denis Saubaméa, Bruno Cohen Salmon, Martine |
Keywords: | Malalties del sistema nerviós central Malalties rares Astròcits Central nervous system diseases Rare diseases Astrocytes |
Issue Date: | 1-Nov-2021 |
Publisher: | eLife Sciences Publications, Ltd |
Abstract: | Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare type of leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes. Perivascular astrocytic processes along with blood vessels form the gliovascular unit. It was not previously known how MLC1 influences the physiology of the gliovascular unit. Here, using the Mlc1 knock-out mouse model of MLC, we demonstrated that MLC1 controls the postnatal development and organization of perivascular astrocytic processes, vascular smooth muscle cell contractility, neurovascular coupling, and intraparenchymal interstitial fluid clearance. Our data suggest that MLC is a developmental disorder of the gliovascular unit, and perivascular astrocytic processes and vascular smooth muscle cell maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease. |
Note: | Reproducció del document publicat a: https://doi.org/10.7554/eLife.71379 |
It is part of: | eLife, 2021, vol. 10, p. e71379 |
URI: | http://hdl.handle.net/2445/181715 |
Related resource: | https://doi.org/10.7554/eLife.71379 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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Megalencephalic leukoencephalopathy.pdf | 16.09 MB | Adobe PDF | View/Open |
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