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showing 10 items of 14051 documents
Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients
2017
In relapsing-remitting multiple sclerosis (RRMS) subtype, the patient's brain itself is capable of repairing the damage, remyelinating the axon and recovering the neurological function. Cerebrospinal fluid (CSF) is in close proximity with brain parenchyma and contains a host of proteins and other molecules, which influence the cellular physiology, that may balance damage and repair of neurons and glial cells. The purpose of this study was to determine the pathophysiological mechanisms underpinning myelin repair in distinct clinical forms of MS and neuromyelitis optica (NMO) patients by studying the effect of diseased CSF on glucose metabolism and ATP synthesis. A cellular model with primary…
The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation.
2016
Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. Furthermore, no plasma membrane receptors for GBPs have been described so far, thus GBPs are still considered orphan neuromodulators. Interestingly, an intricate and controversial f…
An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling
2017
Signaling receptors dynamically exit cilia upon activation of signaling pathways such as Hedgehog. Here, we find that when activated G protein-coupled receptors (GPCRs) fail to undergo BBSome-mediated retrieval from cilia back into the cell, these GPCRs concentrate into membranous buds at the tips of cilia before release into extracellular vesicles named ectosomes. Unexpectedly, actin and the actin regulators drebrin and myosin 6 mediate ectosome release from the tip of cilia. Mirroring signal-dependent retrieval, signal-dependent ectocytosis is a selective and effective process that removes activated signaling molecules from cilia. Congruently, ectocytosis compensates for BBSome defects as…
The FOXP2-Driven Network in Developmental Disorders and Neurodegeneration
2017
The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y) stably overexpressing either human FOXP2 cDNA or its orthologues from the common chimpanzee, Rhesus monkey, and marmoset, respectively. Subsequent RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation. Importantly, RT-qPCR and Western blotting indicated differential re…
How repair-or-dispose decisions under stress can initiate disease progression
2020
Summary Glia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges: By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons. Malfunction of these interactions is implicated in many neurodegenerative diseases. We present a reductionist model that mimics repair-or-dispose decisions to generate a hypothesis for the cause of disease onset. The model assumes four tissue states: healthy and challenged tissue, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. We discuss analogies to progression stages observed in the most common neurodegenerative conditions and…
Evaluation of Planar-Cell-Polarity Phenotypes in Ciliopathy Mouse Mutant Cochlea
2016
In recent years, primary cilia have emerged as key regulators in development and disease by influencing numerous signaling pathways. One of the earliest signaling pathways shown to be associated with ciliary function was the non-canonical Wnt signaling pathway, also referred to as planar cell polarity (PCP) signaling. One of the best places in which to study the effects of planar cell polarity (PCP) signaling during vertebrate development is the mammalian cochlea. PCP signaling disruption in the mouse cochlea disrupts cochlear outgrowth, cellular patterning and hair cell orientation, all of which are affected by cilia dysfunction. The goal of this protocol is to describe the analysis of PCP…
The Role of Nrf2 and PPARγ in the Improvement of Oxidative Stress in Hypertension and Cardiovascular Diseases
2020
Reactive oxygen species are an important element of redox regulation in cells and tissues. During physiological processes, molecules undergo chemical changes caused by reduction and oxidation reactions. Free radicals are involved in interactions with other molecules, leading to oxidative stress. Oxidative stress works two ways depending on the levels of oxidizing agents and products. Excessive action of oxidizing agents damages biomolecules, while a moderate physiological level of oxidative stress (oxidative eustress) is necessary to control life processes through redox signaling required for normal cellular operation. High levels of reactive oxygen species (ROS) mediate pathological change…
Conversion of Nonproliferating Astrocytes into Neurogenic Neural Stem Cells: Control by FGF2 and Interferon-gamma
2016
Abstract Conversion of astrocytes to neurons, via de-differentiation to neural stem cells (NSC), may be a new approach to treat neurodegenerative diseases and brain injuries. The signaling factors affecting such a cell conversion are poorly understood, and they are hard to identify in complex disease models or conventional cell cultures. To address this question, we developed a serum-free, strictly controlled culture system of pure and homogeneous “astrocytes generated from murine embryonic stem cells (ESC).” These stem cell derived astrocytes (mAGES), as well as standard primary astrocytes resumed proliferation upon addition of FGF. The signaling of FGF receptor tyrosine kinase converted G…
Circadian Rhythm in Adipose Tissue: Novel Antioxidant Target for Metabolic and Cardiovascular Diseases
2020
Obesity is a major risk factor for most metabolic and cardiovascular disorders. Adipose tissue is an important endocrine organ that modulates metabolic and cardiovascular health by secreting signaling molecules. Oxidative stress is a common mechanism associated with metabolic and cardiovascular complications including obesity, type 2 diabetes, and hypertension. Oxidative stress can cause adipose tissue dysfunction. Accumulating data from both humans and experimental animal models suggest that adipose tissue function and oxidative stress have an innate connection with the intrinsic biological clock. Circadian clock orchestrates biological processes in adjusting to daily environmental changes…
General Aspects of Metal Ions as Signaling Agents in Health and Disease
2020
This review focuses on the current knowledge on the involvement of metal ions in signaling processes within the cell, in both physiological and pathological conditions. The first section is devoted to the recent discoveries on magnesium and calcium-dependent signal transduction—the most recognized signaling agents among metals. The following sections then describe signaling pathways where zinc, copper, and iron play a key role. There are many systems in which changes in intra- and extra-cellular zinc and copper concentrations have been linked to important downstream events, especially in nervous signal transduction. Iron signaling is mostly related with its homeostasis. However, it is also …