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Drosophila blood brain barrier

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https://www.readbyqxmd.com/read/27708431/attenuation-of-synaptic-toxicity-and-mark4-par1-mediated-tau-phosphorylation-by-methylene-blue-for-alzheimer-s-disease-treatment
#1
Wenchao Sun, Seongsoo Lee, Xiaoran Huang, Song Liu, Mohammed Inayathullah, Kwang-Min Kim, Hongxiang Tang, J Wesson Ashford, Jayakumar Rajadas
Alzheimer's disease (AD) is a neurodegenerative disease characterized by genotypic and phenotypic heterogeneity. Critical components of the two AD pathological pathways, Aβ-amyloidosis and Tauopathy, have been considered as therapeutic targets. Among them, much effort is focused on aberrant Tau phosphorylation and targeting Tau-phosphorylating kinases. Methylene blue (MB), a phenothiazine dye that crosses the blood-brain barrier, has been shown to hit multiple molecular targets involved in AD and have beneficial effects in clinical studies...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27539639/parkinson-disease-linked-gba-mutation-effects-reversed-by-molecular-chaperones-in-human-cell-and-fly-models
#2
Alvaro Sanchez-Martinez, Michelle Beavan, Matthew E Gegg, Kai-Yin Chau, Alexander J Whitworth, Anthony H V Schapira
GBA gene mutations are the greatest cause of Parkinson disease (PD). GBA encodes the lysosomal enzyme glucocerebrosidase (GCase) but the mechanisms by which loss of GCase contributes to PD remain unclear. Inhibition of autophagy and the generation of endoplasmic reticulum (ER) stress are both implicated. Mutant GCase can unfold in the ER and be degraded via the unfolded protein response, activating ER stress and reducing lysosomal GCase. Small molecule chaperones that cross the blood brain barrier help mutant GCase refold and traffic correctly to lysosomes are putative treatments for PD...
August 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27532224/structural-elucidation-of-the-cell-penetrating-penetratin-peptide-in-model-membranes-at-the-atomic-level-probing-hydrophobic-interactions-in-the-blood-brain-barrier
#3
Swapna Bera, Rajiv K Kar, Susanta Mondal, Kalipada Pahan, Anirban Bhunia
Cell-penetrating peptides (CPPs) have shown promise in nonpermeable therapeutic drug delivery, because of their ability to transport a variety of cargo molecules across the cell membranes and their noncytotoxicity. Drosophila antennapedia homeodomain-derived CPP penetratin (RQIKIWFQNRRMKWKK), being rich in positively charged residues, has been increasingly used as a potential drug carrier for various purposes. Penetratin can breach the tight endothelial network known as the blood-brain barrier (BBB), permitting treatment of several neurodegenerative maladies, including Alzheimer's disease, Parkinson's disease, and Huntington's disease...
September 6, 2016: Biochemistry
https://www.readbyqxmd.com/read/27524482/increased-glucose-transport-into-neurons-rescues-a%C3%AE-toxicity-in-drosophila
#4
Teresa Niccoli, Melissa Cabecinha, Anna Tillmann, Fiona Kerr, Chi T Wong, Dalia Cardenes, Alec J Vincent, Lucia Bettedi, Li Li, Sebastian Grönke, Jacqueline Dols, Linda Partridge
Glucose hypometabolism is a prominent feature of the brains of patients with Alzheimer's disease (AD). Disease progression is associated with a reduction in glucose transporters in both neurons and endothelial cells of the blood-brain barrier. However, whether increasing glucose transport into either of these cell types offers therapeutic potential remains unknown. Using an adult-onset Drosophila model of Aβ (amyloid beta) toxicity, we show that genetic overexpression of a glucose transporter, specifically in neurons, rescues lifespan, behavioral phenotypes, and neuronal morphology...
September 12, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27270598/suppression-of-the-motor-deficit-in-a-mucolipidosis-type-iv-mouse-model-by-bone-marrow-transplantation
#5
Marquis T Walker, Craig Montell
Mucolipidosis IV (MLIV) is a severe lysosomal storage disorder, which results from loss of the TRPML1 channel. MLIV causes multiple impairments in young children, including severe motor deficits. Currently, there is no effective treatment. Using a Drosophila MLIV model, we showed previously that introduction of trpml(+ )in phagocytic glia rescued the locomotor deficit by removing early dying neurons, thereby preventing amplification of neuronal death from cytotoxicity. Because microglia, which are phagocytic cells in the mammalian brain, are bone marrow derived, and cross the blood-brain barrier, we used a mouse MLIV model to test the efficacy of bone marrow transplantation (BMT)...
June 7, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27261004/septate-junction-proteins-play-essential-roles-in-morphogenesis-throughout-embryonic-development-in-drosophila
#6
Sonia Hall, Robert E Ward
The septate junction (SJ) is the occluding junction found in the ectodermal epithelia of invertebrate organisms, and is essential to maintain chemically distinct compartments in epithelial organs, to provide the blood-brain barrier in the nervous system, and to provide an important line of defense against invading pathogens. More than 20 genes have been identified to function in the establishment or maintenance of SJs in Drosophila melanogaster Numerous studies have demonstrated the cell biological function of these proteins in establishing the occluding junction, whereas very few studies have examined further developmental roles for them...
2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27098356/imaging-by-elemental-and-molecular-mass-spectrometry-reveals-the-uptake-of-an-arsenolipid-in-the-brain-of-drosophila-melanogaster
#7
Ann-Christin Niehoff, Jacqueline Schulz, Jens Soltwisch, Sören Meyer, Hans Kettling, Michael Sperling, Astrid Jeibmann, Klaus Dreisewerd, Kevin A Francesconi, Tanja Schwerdtle, Uwe Karst
Arsenic-containing lipids (arsenolipids) are natural products of marine organisms such as fish, invertebrates, and algae, many of which are important seafoods. A major group of arsenolipids, namely, the arsenic-containing hydrocarbons (AsHC), have recently been shown to be cytotoxic to human liver and bladder cells, a result that has stimulated interest in the chemistry and toxicology of these compounds. In this study, elemental laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) and molecular matrix-assisted laser desorption/ionization (MALDI-)MS were used to image and quantify the uptake of an AsHC in the model organism Drosophila melanogaster...
May 17, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/26969975/frizzled-receptors-in-development-and-disease
#8
Yanshu Wang, Hao Chang, Amir Rattner, Jeremy Nathans
Frizzled proteins are the principal receptors for the Wnt family of ligands. They mediate canonical Wnt signaling together with Lrp5 and Lrp6 coreceptors. In conjunction with Celsr, Vangl, and a small number of additional membrane and membrane-associated proteins, they also play a central role in tissue polarity/planar cell polarity (PCP) signaling. Targeted mutations in 9 of the 10 mammalian Frizzled genes have revealed their roles in an extraordinarily diverse set of developmental and homeostatic processes, including morphogenetic movements responsible for palate, ventricular septum, ocular furrow, and neural tube closure; survival of thalamic neurons; bone formation; central nervous system (CNS) angiogenesis and blood-brain barrier formation and maintenance; and a wide variety of processes that orient subcellular, cellular, and multicellular structures relative to the body axes...
2016: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/26931464/lovastatin-protects-neurite-degeneration-in-lrrk2-g2019s-parkinsonism-through-activating-the-akt-nrf-pathway-and-inhibiting-gsk3%C3%AE-activity
#9
Chin-Hsien Lin, Han-I Lin, Meng-Ling Chen, Tzu-Ting Lai, Li-Ping Cao, Matthew J Farrer, Ruey-Meei Wu, Cheng-Ting Chien
Parkinson's disease (PD) is a progressive neurodegenerative disorder that lacks a disease-modifying therapy. Leucine-rich repeat kinase 2 (LRRK2) was implicated as the most common genetic cause of PD. We previously established a LRRK2-G2019S Drosophila model that displayed the crucial phenotypes of LRRK2 parkinsonism. Here, we used a two-step approach to identify compounds from the FDA-approved licensed drug library that could suppress neurite degeneration in LRRK2-G2019S parkinsonism. Of 640 compounds, 29 rescued neurite degeneration phenotypes and 3 restored motor disability and dopaminergic neuron loss in aged LRRK2-G2019S flies...
February 29, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/26424032/quantitative-bioimaging-to-investigate-the-uptake-of-mercury-species-in-drosophila-melanogaster
#10
Ann-Christin Niehoff, Oliver Bolle Bauer, Sabrina Kröger, Stefanie Fingerhut, Jacqueline Schulz, Sören Meyer, Michael Sperling, Astrid Jeibmann, Tanja Schwerdtle, Uwe Karst
The uptake of mercury species in the model organism Drosophila melanogaster was investigated by elemental bioimaging using laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS). The mercury distribution in Drosophila melanogaster was analyzed for the three species mercury(II) chloride, methylmercury chloride, and thimerosal after intoxication. A respective analytical method was developed and applied to the analysis of the entire Drosophila melanogaster first, before a particular focus was directed to the cerebral areas of larvae and adult flies...
October 20, 2015: Analytical Chemistry
https://www.readbyqxmd.com/read/26329602/pasiflora-proteins-are-novel-core-components-of-the-septate-junction
#11
Myrto Deligiannaki, Abbie L Casper, Christophe Jung, Ulrike Gaul
Epithelial sheets play essential roles as selective barriers insulating the body from the environment and establishing distinct chemical compartments within it. In invertebrate epithelia, septate junctions (SJs) consist of large multi-protein complexes that localize at the apicolateral membrane and mediate barrier function. Here, we report the identification of two novel SJ components, Pasiflora1 and Pasiflora2, through a genome-wide glial RNAi screen in Drosophila. Pasiflora mutants show permeable blood-brain and tracheal barriers, overelongated tracheal tubes and mislocalization of SJ proteins...
September 1, 2015: Development
https://www.readbyqxmd.com/read/26235423/glial-glycolysis-is-essential-for-neuronal-survival-in-drosophila
#12
Anne Volkenhoff, Astrid Weiler, Matthias Letzel, Martin Stehling, Christian Klämbt, Stefanie Schirmeier
Neuronal information processing requires a large amount of energy, indicating that sugars and other metabolites must be efficiently delivered. However, reliable neuronal function also depends on the maintenance of a constant microenvironment in the brain. Therefore, neurons are efficiently separated from circulation by the blood-brain barrier, and their long axons are insulated by glial processes. At the example of the Drosophila brain, we addressed how sugar is shuttled across the barrier to nurture neurons...
September 1, 2015: Cell Metabolism
https://www.readbyqxmd.com/read/26178654/differentiation-of-drosophila-glial-cells
#13
REVIEW
Sofia Sasse, Helen Neuert, Christian Klämbt
Glial cells are important constituents of the nervous system and a hallmark of these cells are their pronounced migratory abilities. In Drosophila, glial lineages have been well described and some of the molecular mechanisms necessary to guide migrating glial cells to their final target sites have been identified. With the onset of migration, glial cells are already specified into one of five main glial cell types. The perineurial and subperineurial glial cells are eventually located at the outer surface of the Drosophila nervous system and constitute the blood-brain barrier...
November 2015: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/26103549/the-drosophila-blood-brain-barrier-as-interface-between-neurons-and-hemolymph
#14
REVIEW
Stefanie Schirmeier, Christian Klämbt
The blood-brain barrier is an evolutionary ancient structure that provides direct support and protection of the nervous system. In all systems, it establishes a tight diffusion barrier that hinders uncontrolled paracellular diffusion into the nervous system. In invertebrates, the blood-brain barrier separates the nervous system from the hemolymph. Thus, the barrier-forming cells need to actively import ions and nutrients into the nervous system. In addition, metabolic or environmental signals from the external world have to be transmitted across the barrier into the nervous system...
November 2015: Mechanisms of Development
https://www.readbyqxmd.com/read/25742603/death-following-traumatic-brain-injury-in-drosophila-is-associated-with-intestinal-barrier-dysfunction
#15
Rebeccah J Katzenberger, Stanislava Chtarbanova, Stacey A Rimkus, Julie A Fischer, Gulpreet Kaur, Jocelyn M Seppala, Laura C Swanson, Jocelyn E Zajac, Barry Ganetzky, David A Wassarman
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain. Our genome-wide association study of Drosophila melanogaster revealed that the probability of death following TBI is associated with single nucleotide polymorphisms in genes involved in tissue barrier function and glucose homeostasis. We found that TBI causes intestinal and blood-brain barrier dysfunction and that intestinal barrier dysfunction is highly correlated with the probability of death...
2015: ELife
https://www.readbyqxmd.com/read/25452710/the-drosophila-blood-brain-barrier-development-and-function-of-a-glial-endothelium
#16
REVIEW
Stefanie Limmer, Astrid Weiler, Anne Volkenhoff, Felix Babatz, Christian Klämbt
The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells...
2014: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/25440330/targeted-delivery-of-extracellular-matrix-protected-against-neurologic-defects-after-focal-ischemia-reperfusion-in-rats
#17
HongNa Yang, HongLing Yang, YingYun Lu, Shuang Ma, Ying Liu, GuoYong Jia, JianZhong Bi, CuiLan Wang
Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and characterized by defective angiogenesis. The functional sequences (RGDs, GRGDSPASSPISC) derived from fibronectin have been confirmed to augment angiogenesis in vivo and in vitro. However, delivery of peptides into the brain parenchyma has been hampered by the presence of the blood-brain barrier (BBB). We fused RGDs with penetratin (Antp) derived from Drosophila antennapedia homeodomain protein to improve the penetration of peptides through BBB into ischemic hemisphere...
January 2015: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/25426014/the-drosophila-surface-glia-transcriptome-evolutionary-conserved-blood-brain-barrier-processes
#18
Michael K DeSalvo, Samantha J Hindle, Zeid M Rusan, Souvinh Orng, Mark Eddison, Kyle Halliwill, Roland J Bainton
Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable...
2014: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/25275323/delivery-of-circulating-lipoproteins-to-specific-neurons-in-the-drosophila-brain-regulates-systemic-insulin-signaling
#19
Marko Brankatschk, Sebastian Dunst, Linda Nemetschke, Suzanne Eaton
The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation...
2014: ELife
https://www.readbyqxmd.com/read/25200291/control-of-brain-development-and-homeostasis-by-local-and-systemic-insulin-signalling
#20
REVIEW
J Liu, P Spéder, A H Brand
Insulin and insulin-like growth factors (IGFs) are important regulators of growth and metabolism. In both vertebrates and invertebrates, insulin/IGFs are made available to various organs, including the brain, through two routes: the circulating systemic insulin/IGFs act on distant organs via endocrine signalling, whereas insulin/IGF ligands released by local tissues act in a paracrine or autocrine fashion. Although the mechanisms governing the secretion and action of systemic insulin/IGF have been the focus of extensive investigation, the significance of locally derived insulin/IGF has only more recently come to the fore...
September 2014: Diabetes, Obesity & Metabolism
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