Search results for "Molecule"
showing 10 items of 5162 documents
β1-Integrin– and K(V)1.3 channel–dependent signaling stimulates glutamate release from Th17 cells
2020
Although the impact of Th17 cells on autoimmunity is undisputable, their pathogenic effector mechanism is still enigmatic. We discovered soluble N-ethylmaleimide–sensitive factor attachment receptor (SNARE) complex proteins in Th17 cells that enable a vesicular glutamate release pathway that induces local intracytoplasmic calcium release and subsequent damage in neurons. This pathway is glutamine dependent and triggered by binding of β1-integrin to vascular cell adhesion molecule 1 (VCAM-1) on neurons in the inflammatory context. Glutamate secretion could be blocked by inhibiting either glutaminase or K(V)1.3 channels, which are known to be linked to integrin expression and highly expressed…
NOD-like receptors: major players (and targets) in the interface between innate immunity and cancer
2019
Innate immunity comprises several inflammation-related modulatory pathways which receive signals from an array of membrane-bound and cytoplasmic pattern recognition receptors (PRRs). The NLRs (NACHT (NAIP (neuronal apoptosis inhibitor protein), C2TA (MHC class 2 transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TP1 (telomerase-associated protein) and Leucine-Rich Repeat (LRR) domain containing proteins) relate to a large family of cytosolic innate receptors, involved in detection of intracellular pathogens and endogenous byproducts of tissue injury. These receptors may recognize pathogen-associated molecular patterns (PAMPs) and/or danger-associated…
Protein-Free Hapten-Carbon Nanotube Constructs Induce the Secondary Immune Response
2017
Carbon nanotubes are novel technological tools with multiple applications. The interaction between such nanoparticles and living organisms is nowadays a matter of keen research by academic and private institutions. In this study, carbon nanotube constructs were investigated as delivery vehicles for immunostimulation and induction of the secondary immune response to a small organic molecule, namely, a hapten. Two types of nanoconstructs were prepared: on one hand, carbon nanotubes carrying a protein bioconjugate of a hapten covalently linked to the carbon surface, and on the other hand, covalent carbon nanotube constructs of the same model chemical compound without the carrier protein. Nanot…
Alterations in reelin and reelin receptors in Down syndrome.
2019
Reelin is an extracellular matrix glycoprotein that modulates synaptic function and plasticity, with a crucial role in neuronal migration. Changes in the expression of this protein have been reported in neurodegenerative diseases, such as Alzheimer's disease (AD). This molecule is produced by Cajal-Retzius neurons during development and by inhibitory neurons in the adult nervous system. Individuals with Down syndrome (DS) present an early development of AD; therefore, we analyzed the alterations in this molecule and its receptors in the murine model for DS Ts65Dn as well as in human with DS. We performed immunofluorescence analysis for reelin and its receptors very-low-density lipoprotein r…
Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles
2019
Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now…
Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex
2019
Polysialic acid (polySia) is a complex sugar that in the nervous system appears mainly as a posttranslational modification of the neural cell adhesion molecule (NCAM). PolySia plays important roles during brain development, but also in its plasticity during adulthood. Two polysialyltransferases (polyST), ST8SIA2 and ST8SIA4, are involved in the synthesis and attachment of polySia. Both polyST are relevant for developmental migration of cortical interneurons and their establishment in the prefrontal cortex (PFC). In contrast, only ST8SIA4 appears to be important for the structural plasticity of a subpopulation of cortical interneurons in the adult. Interestingly, ST8SIA2 and NCAM are candida…
Lipidomics reveals altered biosynthetic pathways of glycerophospholipids and cell signaling as biomarkers of the polycystic ovary syndrome
2017
// Mariona Jove 1, * , Irene Pradas 1, * , Alba Naudi 1, * , Susana Rovira-Llopis 2 , Celia Banuls 2 , Milagros Rocha 2 , Manuel Portero-Otin 1 , Antonio Hernandez-Mijares 2, 3, 4, # , Victor M. Victor 2, 5, # and Reinald Pamplona 1, # 1 Department of Experimental Medicine, Lleida University-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), 25198 Lleida, Spain 2 Foundation for the Promotion of Healthcare and Biomedical Research in the Valencian Community (FISABIO), Service of Endocrinology, University Hospital Dr. Peset, 46017 Valencia, Spain 3 Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, Valencia University, 46010 Valencia, Spain 4 Department of Medicine, …
Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives
2017
Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”,…
Precision and accuracy of single-molecule FRET measurements-a multi-laboratory benchmark study
2018
Single-molecule Forster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between +/- 0.02 and +/- 0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and…
Small endogenous molecules as moiety to improve targeting of CNS drugs.
2016
A major challenge in the development of novel neuro-therapeutic agents is to effectively overcome the blood-brain barrier (BBB), which acts as a 'working dynamic barrier'. The core problem in the treatment of neurodegenerative diseases is failed delivery of potential medicines due to their inadequate permeation rate. Areas covered: The present review gives a summary of endogenous moieties used in synthesizing prodrugs, derivatives and bioisosteric drugs appositely designed to structurally resemble physiological molecular entities able to be passively absorbed or carried by specific carrier proteins expressed at BBB level. In particular, this overview focuses on aminoacidic, glycosyl, purine…