A5018527847- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemokine receptors and signaling
- HIV Research and Treatment
- RNA Research and Splicing
- Connexins and lens biology
- Ion channel regulation and function
- Immunotherapy and Immune Responses
- interferon and immune responses
- Adenosine and Purinergic Signaling
- Mitochondrial Function and Pathology
- RNA Interference and Gene Delivery
- Neuroscience and Neuropharmacology Research
- T-cell and B-cell Immunology
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Trace Elements in Health
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Retinal Development and Disorders
- Virus-based gene therapy research
- Climate Change Communication and Perception
- Health Education and Validation
- Macrophage Migration Inhibitory Factor
- Caveolin-1 and cellular processes
- Genetics and Neurodevelopmental Disorders
Istituto Superiore di Sanità
2014-2024
As a result of their close association with the blood-brain barrier, astrocytes play an important role in regulating homing different leukocyte subsets to inflamed central nervous system (CNS). In this study, we investigated whether human produce chemokines that promote migration myeloid dendritic cells (DCs). By reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, show cultured stimulated interleukin-1β tumor necrosis factor CCL2, CCL3, CCL4, CCL5, CCL20,...
Abstract To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized expression and functional activity P2 cultured rat progenitors investigated effects ATP its breakdown products on migration proliferation this immature glial cell population. Using Western blot analysis, show that express several P2X (P2X 1,2,3,4,7 ) P2Y (P2Y 1,2,4 receptors. Intracellular Ca 2+ recording by Fura‐2 video imaging allowed to determine rank potency order agonists...
Short QT3 syndrome (SQT3S) is a cardiac disorder characterized by high risk of mortality and associated with mutations in Kir2.1 (KCNJ2) channels. The molecular mechanisms leading to channel dysfunction, rhythm disturbances neurodevelopmental disorders, potentially SQT3S, remain incompletely understood. Here, we report on monozygotic twins displaying short QT interval electrocardiogram recordings autism–epilepsy phenotype. Genetic screening identified novel KCNJ2 variant that (i) enhanced...
Dysfunction of the inwardly-rectifying potassium channels Kir4.1 (KCNJ10) represents a pathogenic mechanism contributing to Autism-Epilepsy comorbidity. To define role variants in disorder, we sequenced KCNJ10 sample affected individuals, and performed genotype-phenotype correlations. The effects mutations on channel activity, protein trafficking, astrocyte function were investigated Xenopus laevis oocytes, human astrocytoma cell lines. An vivo model disorder was also explored through...
Abstract Macrophage inflammatory protein‐3α/CCL20 is a recently identified chemokine that binds to CCR6 and acts as chemoattractant for memory/differentiated T‐cells, B‐cells, immature dendritic cells. We have previously reported CCL20 mRNAs are expressed in the CNS of SJL mice with experimental autoimmune encephalomyelitis (EAE) produced by CNS‐infiltrating leukocytes at disease onset and, additionally, intraparenchymal astrocyte‐like cells during relapses. In this study, we provide further...
Megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare leukodystrophy characterized by macrocephaly, fluid and myelin vacuolation, has been linked to mutations in the MLC1 gene. This gene encodes membrane protein that is highly expressed astrocytes. Based on MLC pathological features, it was proposed astrocyte-mediated defects ion homeostasis could account for alterations observed MLC-affected brains. However, role of effects astrocyte osmoregulatory functions have still be...
Following brain injury, astrocytes express receptors for cytokines and neuropeptides secrete several regulatory mediators that have a well established role in inflammation, immunity, tissue development or repair. To elucidate the of substance P (SP), neurotransmitter peptide tachykinin family, inducing astrocyte secretory activities, we examined expression SP functional consequences their activation cultured from human embryonic spinal cord. Radioligand binding studies revealed only one type...
Megalencephalic leucoencephalopathy with subcortical cysts (MLC) is a rare congenital leucodystrophy caused by mutations in MLC1, membrane protein of unknown function. MLC1 expression astrocyte end-feet contacting blood vessels and meninges, along brain swelling, fluid myelin vacuolation observed MLC patients, suggests possible role for the regulation ion homeostasis cellular volume changes. To identify direct interactors dissect molecular pathways which involved, we used NH2-MLC1 domain as...
Astrocytes are the predominant glial cell population in central nervous system (CNS). Once considered only passive scaffolding elements, astrocytes now recognised as cells playing essential roles CNS development and function. They control extracellular water ion homeostasis, provide substrates for energy metabolism, regulate neurogenesis, myelination synaptic transmission. Due to these multiple activities have been implicated almost all brain pathologies, contributing various aspects of...
Abstract Brain oedema is a life-threatening complication of various neurological conditions. Understanding molecular mechanisms brain volume regulation critical for therapy development. Unique insight comes from monogenic diseases characterized by chronic oedema, which megalencephalic leukoencephalopathy with subcortical cysts (MLC) the prototype. Variants in MLC1 or GLIALCAM, encoding proteins involved astrocyte regulation, are main causes MLC. In some patients, genetic cause remains...
Mutations in the MLC1 gene, which encodes a protein expressed brain astrocytes, are leading cause of MLC, rare leukodystrophy characterized by macrocephaly, edema, subcortical cysts, myelin and astrocyte vacuolation. Although recent studies indicate that is implicated regulation cell volume changes, exact role physiology pathogenesis MLC disease remains to be clarified. In preliminary experiments, we observed was poorly highly proliferating astrocytoma cells when compared with primary...
Loss of function the astrocyte protein MLC1 causes Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC), a leukodystrophy characterized by white matter edema and slow neurological deterioration. dysfunction leads to swelling perivascular endfeet an impaired attachment blood vessels. In isolated primary astrocytes, loss hinders recovery astrocytes from cell swelling, but cellular is not completely understood. modulates gating mechanosensitive ion channels involved in volume...
Astrocytes, the most numerous cells of central nervous system, exert critical functions for brain homeostasis. To this purpose, astrocytes generate a highly interconnected intercellular network allowing rapid exchange ions and metabolites through gap junctions, adjoined channels composed hexamers connexin (Cx) proteins, mainly Cx43. Functional alterations Cxs junctions have been observed in several neuroinflammatory/neurodegenerative diseases. In rare leukodystrophy megalencephalic...
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy caused by mutations in the gene encoding MLC1, membrane protein mainly expressed astrocytes central nervous system. Although MLC1 function unknown, evidence emerging that it may regulate ion fluxes. Using biochemical and proteomic approaches to identify interactors elucidate we found interacts vacuolar ATPase (V-ATPase), proton pump regulates endosomal acidity. Because previously showed intracellular...