ArticleHuman molecular genetics2008
Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 86 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
- Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature.Frontiers in genetics · 2024Article
- 3D MR fingerprinting-derived myelin water fraction characterizing brain development and leukodystrophy.Journal of translational medicine · 2023Article
- GPR37 Receptors and Megalencephalic Leukoencephalopathy with Subcortical Cysts.International journal of molecular sciences · 2022Review
- Ubr1-induced selective endophagy/autophagy protects against the endosomal and CaCellular and molecular life sciences : CMLS · 2022Article
- The neurovascular unit in leukodystrophies: towards solving the puzzle.Fluids and barriers of the CNS · 2022Review
- Emerging cellular themes in leukodystrophies.Frontiers in cell and developmental biology · 2022Review
- Transmembrane topology and oligomeric nature of an astrocytic membrane protein, MLC1.Open biology · 2021Article
- Article
- Cerebellar Astrocyte Transduction as Gene Therapy for Megalencephalic Leukoencephalopathy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- 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
- Mutation-specific peripheral and ER quality control of hERG channel cell-surface expression.Scientific reports · 2019Article
- Structure-guided combination therapy to potently improve the function of mutant CFTRs.Nature medicine · 2018Article
- Leukoencephalopathy-causing CLCN2 mutations are associated with impaired ClThe Journal of physiology · 2017Article
- Megalencephalic leukoencephalopathy with cysts: theAnnals of clinical and translational neurology · 2017Article
- Investigation of LRRC8-Mediated Volume-Regulated Anion Currents in Xenopus Oocytes.Biophysical journal · 2016Article
- Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect.PLoS biology · 2016Article
- MLC1 protein: a likely link between leukodystrophies and brain channelopathies.Frontiers in cellular neuroscience · 2015Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, most often caused by mutations in the MLC1 gene. MLC1 is an oligomeric plasma membrane (PM) protein of unknown function expressed mainly in glial cells and neurons. Most disease-causing missense mutations dramatically reduced the total and PM MLC1 expression levels in Xenopus oocytes and mammalian cells. The impaired expression of the mutants was verified in primary cultures of rat astrocytes, as well as human monocytes, cell types that endogenously express MLC1, demonstrating the relevance of the tissue culture models. Using a combination of biochemical, pharmacological and imaging methods, we also demonstrated that increased endoplasmatic reticulum-associated degradation and endo-lysosomal-associated degradation can contribute to the cell surface expression defect of the mutants. Based on these results, we suggest that MLC1 mutations reduce protein levels in vivo. Since the expression defect of the mutants could be rescued by exposing the mutant-protein expressing cells to low temperature and glycerol, a chemical chaperone, we propose that MLC belongs to the class of conformational diseases. Therefore, we suggest the use of pharmacological strategies that improve MLC1 expression to treat MLC patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.