Search results for "Gli"
showing 10 items of 4824 documents
The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor
2021
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …
Extracellular vesicles in the oligodendrocyte microenvironment
2019
Abstract Extracellular vesicles (EVs) recently took centre stage as mediators of cellular crosstalk modulating the tissue microenvironment. Released by all types of neural cells, EVs may execute a broad spectrum of functions ranging from maintenance of neuronal homeostasis and regulation of neural plasticity to the spread of neurodegenerative agents. Myelinating oligodendrocytes and axons form a highly specialized functional entity that depends on intimate interactions within the oligodendrocyte-neuron niche. EVs released by oligodendrocytes are internalized by neurons in response to neuronal signals and exhibit neuroprotective properties but also may influence other cells present in the mi…
Refining the genetic structure and relationships of European cattle breeds through meta-analysis of worldwide genomic SNP data, focusing on Italian c…
2020
AbstractThe availability of genotyping assays has allowed the detailed evaluation of cattle genetic diversity worldwide. However, these comprehensive studies did not include some local European populations, including autochthonous Italian cattle. In this study, we assembled a large-scale, genome-wide dataset of single nucleotide polymorphisms scored in 3,283 individuals from 205 cattle populations worldwide to assess genome-wide autozygosity and understand better the genetic relationships among these populations. We prioritized European cattle, with a special focus on Italian breeds. Moderate differences in estimates of molecular inbreeding calculated from runs of homozygosity (FROH) were o…
Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology.
2018
Abstract Introduction Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. Aim of the study The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola r…
EBI2 Is Highly Expressed in Multiple Sclerosis Lesions and Promotes Early CNS Migration of Encephalitogenic CD4 T Cells
2017
Arrival of encephalitogenic T cells at inflammatory foci represents a critical step in development of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. EBI2 and its ligand, 7{alpha},25-OHC, direct immune cell localization in secondary lymphoid organs. CH25H and CYP7B1 hydroxylate cholesterol to 7{alpha},25-OHC. During EAE, we found increased expression of CH25H by microglia and CYP7B1 by CNS-infiltrating immune cells elevating the ligand concentration in the CNS. Two critical pro-inflammatory cytokines, interleukin-23 (IL-23) and interleukin-1 beta (IL-1{beta}), maintained expression of EBI2 in differentiating Th17 cells. In line with this, EBI2 enhan…
The iNOS Activity During an Immune Response Controls the CNS Pathology in Experimental Autoimmune Encephalomyelitis
2019
Inducible nitric oxide synthase (iNOS) plays a critical role in the regulation of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Previous studies have shown that iNOS plays pathogenic as well as regulatory roles in MS and EAE. However, how does iNOS alters the pathophysiology of the central nervous system (CNS) in neuronal autoimmunity is not clearly understood. In the present work, we show that treatment of mice with L-NAME, an iNOS inhibitor, during the antigen-priming phase primarily alters brain pathology, while in the subsequent effector phase of the immune response, the spinal cord is involved. Inhibition of iNOS during the priming phase of the immune res…
The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.
2016
KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. M…
Intratumoral Heterogeneity and Longitudinal Changes in Gene Expression Predict Differential Drug Sensitivity in Newly Diagnosed and Recurrent Gliobla…
2020
Background: Inevitable recurrence after radiochemotherapy is the major problem in the treatment of glioblastoma, the most prevalent type of adult brain malignancy. Glioblastomas are notorious for a high degree of intratumor heterogeneity manifest through a diversity of cell types and molecular patterns. The current paradigm of understanding glioblastoma recurrence is that cytotoxic therapy fails to target effectively glioma stem cells. Recent advances indicate that therapy-driven molecular evolution is a fundamental trait associated with glioblastoma recurrence. There is a growing body of evidence indicating that intratumor heterogeneity, longitudinal changes in molecular biomarkers and spe…
Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-"decoy" strategy
2018
MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and …
Quantitative Imaging of D-2-Hydroxyglutarate in Selected Histological Tissue Areas by a Novel Bioluminescence Technique
2016
Abstract Patients with malignant gliomas have a poor prognosis with average survival of less than one year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite, which was discovered first in this tumor entity. D2HG is generated in large amounts due to various “gain-of–function” mutations in the isocitrate dehydrogenases IDH-1 and IDH-2. Meanwhile, D2HG has been detected in se…