ArticleBrain : a journal of neurology2023
Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Written in the Stars: Astrocyte Biology From Evolution to Disease.Acta physiologica (Oxford, England) · 2026Review
- Patient and Family Perspectives on Clinical Outcomes in Therapy Trials in Megalencephalic Leukoencephalopathy with Subcortical Cysts: An Open Inventory.Neuropediatrics · 2026Article
- ROS-Responsive Trifluoperazine Prodrug Nanoparticles and Mesenchymal Stem Cell Exosomes Synergistically Modulate Astrocyte Phenotype for Spinal Cord Injury Repair.ACS applied materials & interfaces · 2026Article
- Multiple molecular mimics in Epstein Barr Nuclear Antigen-1, and the pathogenesis of multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Altered Mechanical Properties of Astrocytes Lacking MLC1: Implications for the Leukodystrophy MLC.Glia · 2026Article
- Megalencephalic leukoencephalopathy with subcortical cysts: a multicenter Italian experience.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Observational
- Time-dependent effects of hypoxia on mitochondrial dynamics, dysfunction and apoptosis in C8-D1A astrocytes.Open life sciences · 2026Article
- Swelling-induced calcium signaling in wild-type andFrontiers in cellular neuroscience · 2026Article
- Megalencephalic Leukoencephalopathy Type 2B.Indian journal of pediatrics · 2026Article
- Article
- Multiple sclerosis: an immune attack on astrocyte-mediated ion and water homeostasis.Nature reviews. Neurology · 2025Review
- 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
- Psychotic attack during the clinical course of megalencephalic leukoencephalopathy with subcortical cysts: a case report.European child & adolescent psychiatry · 2025Article
- Development of perivascular astrocyte processes.Frontiers in neuroscience · 2025Review
- The missense mutation C667F in murine β-dystroglycan causes embryonic lethality, myopathy and blood-brain barrier destabilization.Disease models & mechanisms · 2024Article
- Neurotrauma-From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord.Biomedicines · 2024Review
- Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature.Frontiers in genetics · 2024Article
- Expanding the phenotypic spectrum ofBrain communications · 2024Article
- When brain size matters: novel insights into brain volume control.Brain : a journal of neurology · 2023Article
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Authors and funding
24 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain oedema is a life-threatening complication of various neurological conditions. Understanding molecular mechanisms of brain volume regulation is critical for therapy development. Unique insight comes from monogenic diseases characterized by chronic brain oedema, of which megalencephalic leukoencephalopathy with subcortical cysts (MLC) is the prototype. Variants in MLC1 or GLIALCAM, encoding proteins involved in astrocyte volume regulation, are the main causes of MLC. In some patients, the genetic cause remains unknown. We performed genetic studies to identify novel gene variants in MLC patients, diagnosed by clinical and MRI features, without MLC1 or GLIALCAM variants. We determined subcellular localization of the related novel proteins in cells and in human brain tissue. We investigated functional consequences of the newly identified variants on volume regulation pathways using cell volume measurements, biochemical analysis and electrophysiology. We identified a novel homozygous variant in AQP4, encoding the water channel aquaporin-4, in two siblings, and two de novo heterozygous variants in GPRC5B, encoding the orphan G protein-coupled receptor GPRC5B, in three unrelated patients. The AQP4 variant disrupts membrane localization and thereby channel function. GPRC5B, like MLC1, GlialCAM and aquaporin-4, is expressed in astrocyte endfeet in human brain. Cell volume regulation is disrupted in GPRC5B patient-derived lymphoblasts. GPRC5B functionally interacts with ion channels involved in astrocyte volume regulation. In conclusion, we identify aquaporin-4 and GPRC5B as old and new players in genetic brain oedema. Our findings shed light on the protein complex involved in astrocyte volume regulation and identify GPRC5B as novel potentially druggable target for treating brain oedema.
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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.