Please use this identifier to cite or link to this item:
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
Central nervous system diseases
Rare diseases
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:
It is part of: eLife, 2021, vol. 10, p. e71379
Related resource:
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 SizeFormat 
Megalencephalic leukoencephalopathy.pdf16.09 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons