Search results for " molecule"
showing 10 items of 1523 documents
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”,…
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…
An overview of recent molecular dynamics applications as medicinal chemistry tools for the undruggable site challenge
2018
Molecular dynamics (MD) has become increasingly popular due to the development of hardware and software solutions and the improvement in algorithms, which allowed researchers to scale up calculations in order to speed them up. MD simulations are usually used to address protein folding issues or protein-ligand complex stability through energy profile analysis over time. In recent years, the development of new tools able to deeply explore a potential energy surface (PES) has allowed researchers to focus on the dynamic nature of the binding recognition process and binding-induced protein conformational changes. Moreover, modern approaches have been demonstrated to be effective and reliable in …
Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers
2018
Influenza hemagglutinin (HA) is the canonical type I viral envelope glycoprotein and provides a template for the membrane-fusion mechanisms of numerous viruses. The current model of HA-mediated membrane fusion describes a static "spring-loaded" fusion domain (HA2) at neutral pH. Acidic pH triggers a singular irreversible conformational rearrangement in HA2 that fuses viral and cellular membranes. Here, using single-molecule Förster resonance energy transfer (smFRET)-imaging, we directly visualized pH-triggered conformational changes of HA trimers on the viral surface. Our analyses reveal reversible exchange between the pre-fusion and two intermediate conformations of HA2. Acidification of p…
Extracellular vesicles in food: Experimental evidence of their secretion in grape fruits
2017
In the last decade, the number of studies related with extracellular vesicles (EVs) has dramatically grown since their role as key part of intercellular communication has been confirmed. EVs, as transporter of distinct bioactive molecules, can take part in different physiological mechanisms and have been gaining attention as potential tools with a wide range of therapeutic effects. Whereas a high number of studies have been published related to mammalian derived EVs, including products as food source, the existence of EVs in plants still is controversial. Recent descriptions of vesicles derived from edible plants show that they might contain pharmacological active molecules. In this context…
Regulatory network analysis in estradiol-treated human endothelial cells.
2021
Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a com-prehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miR-NA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17ß- Estradiol (E2) (1 nmol/lL, 24 h). miRNA--mRNA pairings and their associated canonical pat…