ArticleNeurobiology of disease2011
Knockdown of MLC1 in primary astrocytes causes cell vacuolation: a MLC disease cell model.
Article in Neurobiology of disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 74 citations in OpenAlex.
- MLC1 alteration in human iPSCs give rise to disease-like cellular vacuolation phenotype in the astrocyte lineage.Orphanet journal of rare diseases · 2026Article
- Altered Mechanical Properties of Astrocytes Lacking MLC1: Implications for the Leukodystrophy MLC.Glia · 2026Article
- Multiple sclerosis: an immune attack on astrocyte-mediated ion and water homeostasis.Nature reviews. Neurology · 2025Review
- Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature.Frontiers in genetics · 2024Article
- Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain.iScience · 2023Article
- Case report: Analysis of a gene variant and prenatal diagnosis in a family with megalencephalic leukoencephalopathy with subcortical cysts.Frontiers in neurology · 2023Article
- Pharmacological modulation of chloride channels as a therapeutic strategy for neurological disorders.Frontiers in physiology · 2023Review
- Spectrum of sublytic astrocytopathy in neuromyelitis optica.Brain : a journal of neurology · 2022Article
- GPR37 Receptors and Megalencephalic Leukoencephalopathy with Subcortical Cysts.International journal of molecular sciences · 2022Review
- Novel variants causing megalencephalic leukodystrophy in Sudanese families.Journal of human genetics · 2022Article
- Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies.International journal of molecular sciences · 2021Review
- Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations.Scientific reports · 2021Article
- Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic leukoencephalopathy proteins.Human molecular genetics · 2021Article
- Article
- Megalencephalic Leukoencephalopathy: Insights Into Pathophysiology and Perspectives for Therapy.Frontiers in cellular neuroscience · 2020Article
- Plasma membrane localization of MLC1 regulates cellular morphology and motility.Molecular brain · 2019Article
- Megalencephalic Leukoencephalopathy with Subcortical Cysts Protein-1 (MLC1) Counteracts Astrocyte Activation in Response to Inflammatory Signals.Molecular neurobiology · 2019Article
- Leukoencephalopathy-causing CLCN2 mutations are associated with impaired ClThe Journal of physiology · 2017Article
- Stratification of astrocytes in healthy and diseased brain.Brain pathology (Zurich, Switzerland) · 2017Article
- Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms.Acta neuropathologica · 2017Review
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
Abstract
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, in the majority of cases caused by mutations in the MLC1 gene. MRI from MLC patients shows diffuse cerebral white matter signal abnormality and swelling, with evidence of increased water content. Histopathology in a MLC patient shows vacuolation of myelin, which causes the cerebral white matter swelling. MLC1 protein is expressed in astrocytic processes that are part of blood- and cerebrospinal fluid-brain barriers. We aimed to create an astrocyte cell model of MLC disease. The characterization of rat astrocyte cultures revealed MLC1 localization in cell-cell contacts, which contains other proteins described typically in tight and adherent junctions. MLC1 localization in these contacts was demonstrated to depend on the actin cytoskeleton; it was not altered when disrupting the microtubule or the GFAP networks. In human tissues, MLC1 and the protein Zonula Occludens 1 (ZO-1), which is linked to the actin cytoskeleton, co-localized by EM immunostaining and were specifically co-immunoprecipitated. To create an MLC cell model, knockdown of MLC1 in primary astrocytes was performed. Reduction of MLC1 expression resulted in the appearance of intracellular vacuoles. This vacuolation was reversed by the co-expression of human MLC1. Re-examination of a human brain biopsy from an MLC patient revealed that vacuoles were also consistently present in astrocytic processes. Thus, vacuolation of astrocytes is also a hallmark of MLC disease.
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