Search results for "70"
showing 10 items of 9933 documents
The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19
2021
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 over…
Usherin defects lead to early-onset retinal dysfunction in zebrafish
2018
Mutations in USH2A are the most frequent cause of Usher syndrome and autosomal recessive nonsyndromic retinitis pigmentosa. To unravel the pathogenic mechanisms underlying USH2A-associated retinal degeneration and to evaluate future therapeutic strategies that could potentially halt the progression of this devastating disorder, an animal model is needed. The available Ush2a knock-out mouse model does not mimic the human phenotype, because it presents with only a mild and late-onset retinal degeneration. Using CRISPR/Cas9-technology, we introduced protein-truncating germline lesions into the zebrafish ush2a gene (ush2a(rmc1): c.2337_2342delinsAC; p.Cys780GlnfsTer32 and ush2a(b1245): c.15520_…
Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells
2018
SUMMARY Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells. In contrast, ciliopathy patient-derived iPSC-RPE and iPSC-RPE with a knockdown of ciliary-trafficking pr…
Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles
2017
Malignant glioma cells invade the surrounding brain parenchyma, by migrating along the blood vessels, thus promoting cancer growth. The biological bases of these activities are grounded in profound alterations of the metabolism and the structural organization of the cells, which consequently acquire the ability to modify the surrounding microenvironment, by altering the extracellular matrix and affecting the properties of the other cells present in the brain, such as normal glial-, endothelial- and immune-cells. Most of the effects on the surrounding environment are probably exerted through the release of a variety of extracellular vesicles (EVs), which contain many different classes of mol…
Cnidarian Immunity and the Repertoire of Defense Mechanisms in Anthozoans
2020
Anthozoa is the most specious class of the phylum Cnidaria that is phylogenetically basal within the Metazoa. It is an interesting group for studying the evolution of mutualisms and immunity, for despite their morphological simplicity, Anthozoans are unexpectedly immunologically complex, with large genomes and gene families similar to those of the Bilateria. Evidence indicates that the Anthozoan innate immune system is not only involved in the disruption of harmful microorganisms, but is also crucial in structuring tissue-associated microbial communities that are essential components of the cnidarian holobiont and useful to the animal’s health for several functions including metabolism, imm…
Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia—Relevance for Mental Diseases
2021
The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor–receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biologica…
Invariant NKT Cells and Rheumatic Disease: Focus on Primary Sjogren Syndrome.
2019
Primary Sjogren syndrome (pSS) is a complex autoimmune disease mainly affecting salivary and lacrimal glands. Several factors contribute to pSS pathogenesis; in particular, innate immunity seems to play a key role in disease etiology. Invariant natural killer (NK) T cells (iNKT) are a T-cell subset able to recognize glycolipid antigens. Their function remains unclear, but studies have pointed out their ability to modulate the immune system through the promotion of specific cytokine milieu. In this review, we discussed the possible role of iNKT in pSS development, as well as their implications as future markers of disease activity.
Interaction of Intestinal Bacteria with Human Rotavirus during Infection in Children
2021
The gut microbiota has emerged as a key factor in the pathogenesis of intestinal viruses, including enteroviruses, noroviruses and rotaviruses (RVs), where stimulatory and inhibitory effects on infectivity have been reported. With the aim of determining whether members of the microbiota interact with RVs during infection, a combination of anti-RV antibody labeling, fluorescence-activated cell sorting and 16S rRNA amplicon sequencing was used to characterize the interaction between specific bacteria and RV in stool samples of children suffering from diarrhea produced by G1P[8] RV. The genera Ruminococcus and Oxalobacter were identified as RV binders in stools, displaying enrichments between …
Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery
2020
Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expr…
Starvation resistance and tissue-specific gene expression of stress-related genes in a naturally inbred ant population
2016
Starvation is one of the most common and severe stressors in nature. Not only does it lead to death if not alleviated, it also forces the starved individual to allocate resources only to the most essential processes. This creates energetic trade-offs which can lead to many secondary challenges for the individual. These energetic trade-offs could be exacerbated in inbred individuals, which have been suggested to have a less efficient metabolism. Here, we studied the effect of inbreeding on starvation resistance in a natural population of Formica exsecta ants, with a focus on survival and tissue-specific expression of stress, metabolism and immunity-related genes. Starvation led to large tis…