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  1. Article ; Online: Author Correction: IL-10 based immunomodulation initiated at birth extends lifespan in a familial mouse model of amyotrophic lateral sclerosis.

    Strickland, Michael R / Ibanez, Kristen R / Yaroshenko, Mariya / Diaz, Carolina Ceballos / Borchelt, David R / Chakrabarty, Paramita

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 3396

    Language English
    Publishing date 2021-02-03
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-83092-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: IL-10 based immunomodulation initiated at birth extends lifespan in a familial mouse model of amyotrophic lateral sclerosis.

    Strickland, Michael R / Ibanez, Kristen R / Yaroshenko, Mariya / Diaz, Carolina Ceballos / Borchelt, David R / Chakrabarty, Paramita

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 20862

    Abstract: Inflammatory signaling is thought to modulate the neurodegenerative cascade in amyotrophic lateral sclerosis (ALS). We have previously shown that expression of Interleukin-10 (IL-10), a classical anti-inflammatory cytokine, extends lifespan in the SOD1- ... ...

    Abstract Inflammatory signaling is thought to modulate the neurodegenerative cascade in amyotrophic lateral sclerosis (ALS). We have previously shown that expression of Interleukin-10 (IL-10), a classical anti-inflammatory cytokine, extends lifespan in the SOD1-G93A mouse model of familial ALS. Here we test whether co-expression of the decoy chemokine receptor M3, that can scavenge inflammatory chemokines, augments the efficacy of IL-10. We found that recombinant adeno-associated virus (AAV)-mediated expression of IL-10, alone, or in combination with M3, resulted in modest extension of lifespan relative to control SOD1-G93A cohort. Interestingly neither AAV-M3 alone nor AAV-IL-10 + AAV-M3 extend survival beyond that of the AAV-IL-10 alone cohort. Focused transcriptomic analysis revealed induction of innate immunity and phagocytotic pathways in presymptomatic SOD1-G93A mice expressing IL-10 + M3 or IL-10 alone. Further, while IL-10 expression increased microglial burden, the IL-10 + M3 group showed lower microglial burden, suggesting that M3 can successfully lower microgliosis before disease onset. Our data demonstrates that over-expression of an anti-inflammatory cytokine and a decoy chemokine receptor can modulate inflammatory processes in SOD1-G93A mice, modestly delaying the age to paralysis. This suggests that multiple inflammatory pathways can be targeted simultaneously in neurodegenerative disease and supports consideration of adapting these approaches to treatment of ALS and related disorders.
    MeSH term(s) Amyotrophic Lateral Sclerosis/immunology ; Animals ; Dependovirus/immunology ; Disease Models, Animal ; Female ; Immunity, Innate/immunology ; Immunomodulation/immunology ; Inflammation/immunology ; Interleukin-10/immunology ; Longevity/immunology ; Male ; Mice ; Mice, Inbred C3H ; Mice, Transgenic ; Microglia/immunology ; Neurodegenerative Diseases/immunology ; Phagocytosis/immunology ; Signal Transduction/immunology ; Superoxide Dismutase-1/immunology
    Chemical Substances IL10 protein, mouse ; Interleukin-10 (130068-27-8) ; Superoxide Dismutase-1 (EC 1.15.1.1)
    Language English
    Publishing date 2020-11-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-77564-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

    Sims, Rebecca / van der Lee, Sven J / Naj, Adam C / Bellenguez, Céline / Badarinarayan, Nandini / Jakobsdottir, Johanna / Kunkle, Brian W / Boland, Anne / Raybould, Rachel / Bis, Joshua C / Martin, Eden R / Grenier-Boley, Benjamin / Heilmann-Heimbach, Stefanie / Chouraki, Vincent / Kuzma, Amanda B / Sleegers, Kristel / Vronskaya, Maria / Ruiz, Agustin / Graham, Robert R /
    Olaso, Robert / Hoffmann, Per / Grove, Megan L / Vardarajan, Badri N / Hiltunen, Mikko / Nöthen, Markus M / White, Charles C / Hamilton-Nelson, Kara L / Epelbaum, Jacques / Maier, Wolfgang / Choi, Seung-Hoan / Beecham, Gary W / Dulary, Cécile / Herms, Stefan / Smith, Albert V / Funk, Cory C / Derbois, Céline / Forstner, Andreas J / Ahmad, Shahzad / Li, Hongdong / Bacq, Delphine / Harold, Denise / Satizabal, Claudia L / Valladares, Otto / Squassina, Alessio / Thomas, Rhodri / Brody, Jennifer A / Qu, Liming / Sánchez-Juan, Pascual / Morgan, Taniesha / Wolters, Frank J / Zhao, Yi / Garcia, Florentino Sanchez / Denning, Nicola / Fornage, Myriam / Malamon, John / Naranjo, Maria Candida Deniz / Majounie, Elisa / Mosley, Thomas H / Dombroski, Beth / Wallon, David / Lupton, Michelle K / Dupuis, Josée / Whitehead, Patrice / Fratiglioni, Laura / Medway, Christopher / Jian, Xueqiu / Mukherjee, Shubhabrata / Keller, Lina / Brown, Kristelle / Lin, Honghuang / Cantwell, Laura B / Panza, Francesco / McGuinness, Bernadette / Moreno-Grau, Sonia / Burgess, Jeremy D / Solfrizzi, Vincenzo / Proitsi, Petra / Adams, Hieab H / Allen, Mariet / Seripa, Davide / Pastor, Pau / Cupples, L Adrienne / Price, Nathan D / Hannequin, Didier / Frank-García, Ana / Levy, Daniel / Chakrabarty, Paramita / Caffarra, Paolo / Giegling, Ina / Beiser, Alexa S / Giedraitis, Vilmantas / Hampel, Harald / Garcia, Melissa E / Wang, Xue / Lannfelt, Lars / Mecocci, Patrizia / Eiriksdottir, Gudny / Crane, Paul K / Pasquier, Florence / Boccardi, Virginia / Henández, Isabel / Barber, Robert C / Scherer, Martin / Tarraga, Lluis / Adams, Perrie M / Leber, Markus / Chen, Yuning / Albert, Marilyn S / Riedel-Heller, Steffi / Emilsson, Valur / Beekly, Duane / Braae, Anne / Schmidt, Reinhold / Blacker, Deborah / Masullo, Carlo / Schmidt, Helena / Doody, Rachelle S / Spalletta, Gianfranco / Longstreth, W T / Fairchild, Thomas J / Bossù, Paola / Lopez, Oscar L / Frosch, Matthew P / Sacchinelli, Eleonora / Ghetti, Bernardino / Yang, Qiong / Huebinger, Ryan M / Jessen, Frank / Li, Shuo / Kamboh, M Ilyas / Morris, John / Sotolongo-Grau, Oscar / Katz, Mindy J / Corcoran, Chris / Dunstan, Melanie / Braddel, Amy / Thomas, Charlene / Meggy, Alun / Marshall, Rachel / Gerrish, Amy / Chapman, Jade / Aguilar, Miquel / Taylor, Sarah / Hill, Matt / Fairén, Mònica Díez / Hodges, Angela / Vellas, Bruno / Soininen, Hilkka / Kloszewska, Iwona / Daniilidou, Makrina / Uphill, James / Patel, Yogen / Hughes, Joseph T / Lord, Jenny / Turton, James / Hartmann, Annette M / Cecchetti, Roberta / Fenoglio, Chiara / Serpente, Maria / Arcaro, Marina / Caltagirone, Carlo / Orfei, Maria Donata / Ciaramella, Antonio / Pichler, Sabrina / Mayhaus, Manuel / Gu, Wei / Lleó, Alberto / Fortea, Juan / Blesa, Rafael / Barber, Imelda S / Brookes, Keeley / Cupidi, Chiara / Maletta, Raffaele Giovanni / Carrell, David / Sorbi, Sandro / Moebus, Susanne / Urbano, Maria / Pilotto, Alberto / Kornhuber, Johannes / Bosco, Paolo / Todd, Stephen / Craig, David / Johnston, Janet / Gill, Michael / Lawlor, Brian / Lynch, Aoibhinn / Fox, Nick C / Hardy, John / Albin, Roger L / Apostolova, Liana G / Arnold, Steven E / Asthana, Sanjay / Atwood, Craig S / Baldwin, Clinton T / Barnes, Lisa L / Barral, Sandra / Beach, Thomas G / Becker, James T / Bigio, Eileen H / Bird, Thomas D / Boeve, Bradley F / Bowen, James D / Boxer, Adam / Burke, James R / Burns, Jeffrey M / Buxbaum, Joseph D / Cairns, Nigel J / Cao, Chuanhai / Carlson, Chris S / Carlsson, Cynthia M / Carney, Regina M / Carrasquillo, Minerva M / Carroll, Steven L / Diaz, Carolina Ceballos / Chui, Helena C / Clark, David G / Cribbs, David H / Crocco, Elizabeth A / DeCarli, Charles / Dick, Malcolm / Duara, Ranjan / Evans, Denis A / Faber, Kelley M / Fallon, Kenneth B / Fardo, David W / Farlow, Martin R / Ferris, Steven / Foroud, Tatiana M / Galasko, Douglas R / Gearing, Marla / Geschwind, Daniel H / Gilbert, John R / Graff-Radford, Neill R / Green, Robert C / Growdon, John H / Hamilton, Ronald L / Harrell, Lindy E / Honig, Lawrence S / Huentelman, Matthew J / Hulette, Christine M / Hyman, Bradley T / Jarvik, Gail P / Abner, Erin / Jin, Lee-Way / Jun, Gyungah / Karydas, Anna / Kaye, Jeffrey A / Kim, Ronald / Kowall, Neil W / Kramer, Joel H / LaFerla, Frank M / Lah, James J / Leverenz, James B / Levey, Allan I / Li, Ge / Lieberman, Andrew P / Lunetta, Kathryn L / Lyketsos, Constantine G / Marson, Daniel C / Martiniuk, Frank / Mash, Deborah C / Masliah, Eliezer / McCormick, Wayne C / McCurry, Susan M / McDavid, Andrew N / McKee, Ann C / Mesulam, Marsel / Miller, Bruce L / Miller, Carol A / Miller, Joshua W / Morris, John C / Murrell, Jill R / Myers, Amanda J / O'Bryant, Sid / Olichney, John M / Pankratz, Vernon S / Parisi, Joseph E / Paulson, Henry L / Perry, William / Peskind, Elaine / Pierce, Aimee / Poon, Wayne W / Potter, Huntington / Quinn, Joseph F / Raj, Ashok / Raskind, Murray / Reisberg, Barry / Reitz, Christiane / Ringman, John M / Roberson, Erik D / Rogaeva, Ekaterina / Rosen, Howard J / Rosenberg, Roger N / Sager, Mark A / Saykin, Andrew J / Schneider, Julie A / Schneider, Lon S / Seeley, William W / Smith, Amanda G / Sonnen, Joshua A / Spina, Salvatore / Stern, Robert A / Swerdlow, Russell H / Tanzi, Rudolph E / Thornton-Wells, Tricia A / Trojanowski, John Q / Troncoso, Juan C / Van Deerlin, Vivianna M / Van Eldik, Linda J / Vinters, Harry V / Vonsattel, Jean Paul / Weintraub, Sandra / Welsh-Bohmer, Kathleen A / Wilhelmsen, Kirk C / Williamson, Jennifer / Wingo, Thomas S / Woltjer, Randall L / Wright, Clinton B / Yu, Chang-En / Yu, Lei / Garzia, Fabienne / Golamaully, Feroze / Septier, Gislain / Engelborghs, Sebastien / Vandenberghe, Rik / De Deyn, Peter P / Fernadez, Carmen Muñoz / Benito, Yoland Aladro / Thonberg, Hakan / Forsell, Charlotte / Lilius, Lena / Kinhult-Stählbom, Anne / Kilander, Lena / Brundin, RoseMarie / Concari, Letizia / Helisalmi, Seppo / Koivisto, Anne Maria / Haapasalo, Annakaisa / Dermecourt, Vincent / Fievet, Nathalie / Hanon, Olivier / Dufouil, Carole / Brice, Alexis / Ritchie, Karen / Dubois, Bruno / Himali, Jayanadra J / Keene, C Dirk / Tschanz, JoAnn / Fitzpatrick, Annette L / Kukull, Walter A / Norton, Maria / Aspelund, Thor / Larson, Eric B / Munger, Ron / Rotter, Jerome I / Lipton, Richard B / Bullido, María J / Hofman, Albert / Montine, Thomas J / Coto, Eliecer / Boerwinkle, Eric / Petersen, Ronald C / Alvarez, Victoria / Rivadeneira, Fernando / Reiman, Eric M / Gallo, Maura / O'Donnell, Christopher J / Reisch, Joan S / Bruni, Amalia Cecilia / Royall, Donald R / Dichgans, Martin / Sano, Mary / Galimberti, Daniela / St George-Hyslop, Peter / Scarpini, Elio / Tsuang, Debby W / Mancuso, Michelangelo / Bonuccelli, Ubaldo / Winslow, Ashley R / Daniele, Antonio / Wu, Chuang-Kuo / Peters, Oliver / Nacmias, Benedetta / Riemenschneider, Matthias / Heun, Reinhard / Brayne, Carol / Rubinsztein, David C / Bras, Jose / Guerreiro, Rita / Al-Chalabi, Ammar / Shaw, Christopher E / Collinge, John / Mann, David / Tsolaki, Magda / Clarimón, Jordi / Sussams, Rebecca / Lovestone, Simon / O'Donovan, Michael C / Owen, Michael J / Behrens, Timothy W / Mead, Simon / Goate, Alison M / Uitterlinden, Andre G / Holmes, Clive / Cruchaga, Carlos / Ingelsson, Martin / Bennett, David A / Powell, John / Golde, Todd E / Graff, Caroline / De Jager, Philip L / Morgan, Kevin / Ertekin-Taner, Nilufer / Combarros, Onofre / Psaty, Bruce M / Passmore, Peter / Younkin, Steven G / Berr, Claudine / Gudnason, Vilmundur / Rujescu, Dan / Dickson, Dennis W / Dartigues, Jean-François / DeStefano, Anita L / Ortega-Cubero, Sara / Hakonarson, Hakon / Campion, Dominique / Boada, Merce / Kauwe, John Keoni / Farrer, Lindsay A / Van Broeckhoven, Christine / Ikram, M Arfan / Jones, Lesley / Haines, Jonathan L / Tzourio, Christophe / Launer, Lenore J / Escott-Price, Valentina / Mayeux, Richard / Deleuze, Jean-François / Amin, Najaf / Holmans, Peter A / Pericak-Vance, Margaret A / Amouyel, Philippe / van Duijn, Cornelia M / Ramirez, Alfredo / Wang, Li-San / Lambert, Jean-Charles / Seshadri, Sudha / Williams, Julie / Schellenberg, Gerard D

    Nature genetics

    2017  Volume 49, Issue 9, Page(s) 1373–1384

    Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × ... ...

    Abstract We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Alzheimer Disease/genetics ; Amino Acid Sequence ; Case-Control Studies ; Exome/genetics ; Gene Expression Profiling ; Gene Frequency ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Immunity, Innate/genetics ; Linkage Disequilibrium ; Membrane Glycoproteins/genetics ; Microglia/metabolism ; Odds Ratio ; Phospholipase C gamma/genetics ; Polymorphism, Single Nucleotide ; Protein Interaction Maps/genetics ; Receptors, Immunologic/genetics ; Sequence Homology, Amino Acid
    Chemical Substances ABI3 protein, human ; Adaptor Proteins, Signal Transducing ; Membrane Glycoproteins ; Receptors, Immunologic ; TREM2 protein, human ; Phospholipase C gamma (EC 3.1.4.3)
    Language English
    Publishing date 2017-07-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.3916
    Database MEDical Literature Analysis and Retrieval System OnLINE

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