The Contributions of Microglial Vps35 to Adult Hippocampal Neurogenesis and Neurodegenerative Disorders
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DF2589-MUL1 Antibody
Affinity Biosciences website:www.affbiotech.com order:[email protected] MUL1 Antibody Cat.#: DF2589 Concn.: 1mg/ml Mol.Wt.: 38 kDa Size: 50ul,100ul,200ul Source: Rabbit Clonality: Polyclonal Application: WB 1:500-1:2000, ELISA(peptide) 1:20000-1:40000 *The optimal dilutions should be determined by the end user. Reactivity: Human,Mouse,Rat Purification: The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific). Specificity: MUL1 Antibody detects endogenous levels of total MUL1. Immunogen: A synthesized peptide derived from human MUL1, corresponding to a region within the internal amino acids. Uniprot: Q969V5 Description: Exhibits weak E3 ubiquitin-protein ligase activity, but preferentially acts as a SUMO E3 ligase at physiological concentrations. Plays a role in the control of mitochondrial morphology. Promotes mitochondrial fragmentation and influences mitochondrial localization. Inhibits cell growth. When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. Storage Condition and Rabbit IgG in phosphate buffered saline, pH 7.4, 150mM Buffer: NaCl, 0.02% sodium azide and 50% glycerol. Western blot analysis of extracts from various samples, using MUL1 Antibody. Lane 1: Rat liver, blocked with antigen-specific peptides, Lane 2: Rat liver, Lane 3: Hela cells. 1 / 2 Affinity Biosciences website:www.affbiotech.com order:[email protected] Western blot analysis of MUL1 expression in A431 whole cell lysates ,The lane on the left was treated with the antigen- specific peptide. -
TREM2 Regulates Innate Immunity in Alzheimer's Disease
Li and Zhang Journal of Neuroinflammation (2018) 15:107 https://doi.org/10.1186/s12974-018-1148-y REVIEW Open Access TREM2 regulates innate immunity in Alzheimer’s disease Jiang-Tao Li and Ying Zhang* Abstract Recent research has shown that the triggering receptor expressed on myeloid cells 2 (TREM2) in microglia is closely related to the pathogenesis of Alzheimer’s disease (AD). The mechanism of this relationship, however, remains unclear. TREM2 is part of the TREM family of receptors, which are expressed primarily in myeloid cells, including monocytes, dendritic cells, and microglia. The TREM family members are cell surface glycoproteins with an immunoglobulin-like extracellular domain, a transmembrane region and a short cytoplasmic tail region. The present article reviews the following: (1) the structure, function, and variant site analysis of the Trem2 gene; (2) the metabolism of TREM2 in peripheral blood and cerebrospinal fluid; and (3) the possible underlying mechanism by which TREM2 regulates innate immunity and participates in AD. Keywords: Alzheimer’s disease (AD), Triggering receptor expressed on myeloid cells 2 (TREM2), Innate immunity, Inflammation Background and keep our bodies healthy. Innate immunity has been Alzheimer’s disease (AD) is the most common age- gradually established during the long-term process of evo- related neurodegenerative disease. The early symptoms lution. Over the past few years, genetic research has found of AD are short-term memory loss and disorientation, some new pathogenic factors associated with AD [3]. In the followed by progressive memory loss and irreversible analysis of these factors, the innate immune system has cognitive decline. As AD progresses, severe clinical attracted a great deal of attention, especially regarding the neuropsychiatric symptoms appear, and the patients can function of microglia [4]. -
MUL1 Polyclonal Antibody Catalog Number PA5-29550 Product Data Sheet
Lot Number: TE2564971L Website: thermofisher.com Customer Service (US): 1 800 955 6288 ext. 1 Technical Support (US): 1 800 955 6288 ext. 441 thermofisher.com/contactus MUL1 Polyclonal Antibody Catalog Number PA5-29550 Product Data Sheet Details Species Reactivity Size 100 µL Tested species reactivity Human Host / Isotype Rabbit IgG Tested Applications Dilution * Class Polyclonal Immunocytochemistry (ICC) 1:100-1:1000 Type Antibody Immunofluorescence (IF) 1:100-1:1000 Recombinant fragment Immunohistochemistry (Paraffin) Immunogen corresponding to a region within 1:100-1:1000 amino acids 1 and 352 of Human (IHC (P)) MUL1 Western Blot (WB) 1:500-1:3000 Conjugate Unconjugated * Suggested working dilutions are given as a guide only. It is recommended that the user titrate the product for use in their Form Liquid own experiment using appropriate negative and positive controls. Concentration 1.34mg/ml Purification Antigen affinity chromatography Storage Buffer PBS, pH 7, with 1% BSA, 20% glycerol Contains 0.025% Proclin 300 Storage Conditions -20° C, Avoid Freeze/Thaw Cycles Product Specific Information PA5-29550 targets MUL1 in IF and WB applications and shows reactivity with Human samples. The PA5-29550 immunogen is recombinant fragment corresponding to a region within amino acids 1 and 352 of Human MUL1. Background/Target Information E3 ubiquitin-protein ligase that plays a role in the control of mitochondrial morphology. Promotes mitochondrial fragmentation and influences mitochondrial localization. Inhibits cell growth. When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. -
Significantly Enriched Gene Ontology Terms of the Hub Genes. (B) Significantly Enriched Kyoto Encyclopedia of Genes and Genomes Pathways of the Hub Genes
Figure S1. Functional enrichment analysis of hub genes. (A) Significantly enriched Gene Ontology terms of the hub genes. (B) Significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways of the hub genes. Th, T helper cell. Table SI. List of metagenes for the 25 immune cell subpopulations. Metagene Immune cell type Immunity ADAM28 Activated B cell Adaptive CD180 Activated B cell Adaptive CD79B Activated B cell Adaptive BLK Activated B cell Adaptive CD19 Activated B cell Adaptive MS4A1 Activated B cell Adaptive TNFRSF17 Activated B cell Adaptive IGHM Activated B cell Adaptive GNG7 Activated B cell Adaptive MICAL3 Activated B cell Adaptive SPIB Activated B cell Adaptive HLA-DOB Activated B cell Adaptive IGKC Activated B cell Adaptive PNOC Activated B cell Adaptive FCRL2 Activated B cell Adaptive BACH2 Activated B cell Adaptive CR2 Activated B cell Adaptive TCL1A Activated B cell Adaptive AKNA Activated B cell Adaptive ARHGAP25 Activated B cell Adaptive CCL21 Activated B cell Adaptive CD27 Activated B cell Adaptive CD38 Activated B cell Adaptive CLEC17A Activated B cell Adaptive CLEC9A Activated B cell Adaptive CLECL1 Activated B cell Adaptive AIM2 Activated CD4 T cell Adaptive BIRC3 Activated CD4 T cell Adaptive BRIP1 Activated CD4 T cell Adaptive CCL20 Activated CD4 T cell Adaptive CCL4 Activated CD4 T cell Adaptive CCL5 Activated CD4 T cell Adaptive CCNB1 Activated CD4 T cell Adaptive CCR7 Activated CD4 T cell Adaptive DUSP2 Activated CD4 T cell Adaptive ESCO2 Activated CD4 T cell Adaptive ETS1 Activated CD4 T cell Adaptive EXO1 -
Prior Activation State Shapes the Microglia Response to Antihuman TREM2 in a Mouse Model of Alzheimer’S Disease
Prior activation state shapes the microglia response to antihuman TREM2 in a mouse model of Alzheimer’s disease Daniel C. Ellwangera,1, Shoutang Wangb,1, Simone Brioschib, Zhifei Shaoc, Lydia Greend, Ryan Casee, Daniel Yoof, Dawn Weishuhnd, Palaniswami Rathanaswamid, Jodi Bradleyg, Sara Raoc, Diana Chag, Peng Luanh, Shilpa Sambashivana, Susan Gilfillanb, Samuel A. Hassong, Ian N. Foltzd, Menno van Lookeren Campagnec,2, and Marco Colonnab,2 aGenome Analysis Unit, Amgen Research, Amgen Inc., South San Francisco, CA 94080; bDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110; cDepartment of Inflammation and Oncology, Amgen Research, Amgen Inc., South San Francisco, CA 94080; dDepartment of Biologics Discovery, Amgen Research, Amgen Inc., Burnaby, BC, V5A1V7 Canada; eDiscovery Attribute Sciences, Amgen Research, Amgen Inc., South San Francisco, CA 94080; fDepartment of Biologics Optimization, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320; gDepartment of Neuroscience, Amgen Research, Amgen Inc., Cambridge, MA 02142; and hDepartment of Translational Safety and Bioanalytical Sciences, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320. Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved November 30, 2020 (received for review August 20, 2020) Triggering receptor expressed on myeloid cells 2 (TREM2) sustains accumulation also elicits a response by microglia, brain resident microglia response to brain injury stimuli including apoptotic cells, macrophages that support the development, function, and im- myelin damage, and amyloid β (Aβ). Alzheimer’s disease (AD) risk mune defense of the CNS (3). is associated with the TREM2R47H variant, which impairs ligand While all dominant mutations causing familial early-onset AD binding and consequently microglia responses to Aβ pathology. -
Efficacy and Mechanistic Evaluation of Tic10, a Novel Antitumor Agent
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2012 Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent Joshua Edward Allen University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Oncology Commons Recommended Citation Allen, Joshua Edward, "Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent" (2012). Publicly Accessible Penn Dissertations. 488. https://repository.upenn.edu/edissertations/488 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/488 For more information, please contact [email protected]. Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent Abstract TNF-related apoptosis-inducing ligand (TRAIL; Apo2L) is an endogenous protein that selectively induces apoptosis in cancer cells and is a critical effector in the immune surveillance of cancer. Recombinant TRAIL and TRAIL-agonist antibodies are in clinical trials for the treatment of solid malignancies due to the cancer-specific cytotoxicity of TRAIL. Recombinant TRAIL has a short serum half-life and both recombinant TRAIL and TRAIL receptor agonist antibodies have a limited capacity to perfuse to tissue compartments such as the brain, limiting their efficacy in certain malignancies. To overcome such limitations, we searched for small molecules capable of inducing the TRAIL gene using a high throughput luciferase reporter gene assay. We selected TRAIL-inducing compound 10 (TIC10) for further study based on its induction of TRAIL at the cell surface and its promising therapeutic index. TIC10 is a potent, stable, and orally active antitumor agent that crosses the blood-brain barrier and transcriptionally induces TRAIL and TRAIL-mediated cell death in a p53-independent manner. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Novel TREM2 Splicing Isoform That Lacks the V-Set Immunoglobulin Domain Is Abundant In
bioRxiv preprint doi: https://doi.org/10.1101/2020.11.30.404897; this version posted December 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Novel TREM2 splicing isoform that lacks the V-set immunoglobulin domain is abundant in the human brain. Kostantin Kiianitsa1, Irina Kurtz2, Neal Beeman2, Mark Matsushita2, Wei-Ming Chien2, Wendy H. Raskind2,3,4,5, Olena Korvatska3* 1 Department of Immunology, University of Washington, Seattle, USA. 2 Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, USA. 3 Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA 4 Mental Illness Research, Education and Clinical Center (MIRECC), VA Puget Sound Medical Center, Seattle, USA 5 Geriatric Research, Education and Clinical Center (GRECC), VA Puget Sound Medical Center, Seattle, USA * corresponding author ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.11.30.404897; this version posted December 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract TREM2 is an immunoglobulin-like receptor expressed by certain myeloid cells, such as macrophages, dendritic cells, osteoclasts and microglia. In the brain, TREM2 plays an important role in the immune function of microglia, and its dysfunction is linked to various neurodegenerative conditions in humans. -
Reporter Cell Assay for Human CD33 Validated by Specific Antibodies And
www.nature.com/scientificreports OPEN Reporter cell assay for human CD33 validated by specifc antibodies and human iPSC‑derived microglia Jannis Wißfeld1, Mona Mathews1,4, Omar Mossad1, Paola Picardi2, Alessandro Cinti2, Loredana Redaelli2, Laurent Pradier3, Oliver Brüstle1,4 & Harald Neumann1* CD33/Sialic acid‑binding Ig‑like lectin 3 (SIGLEC3) is an innate immune receptor expressed on myeloid cells and mediates inhibitory signaling via tyrosine phosphatases. Variants of CD33 are associated with Alzheimer’s disease (AD) suggesting that modulation of CD33 signaling might be benefcial in AD. Hence, there is an urgent need for reliable cellular CD33 reporter systems. Therefore, we generated a CD33 reporter cell line expressing a fusion protein consisting of the extracellular domain of either human full‑length CD33 (CD33M) or the AD‑protective variant CD33ΔE2 (D2‑CD33/CD33m) linked to TYRO protein tyrosine kinase binding protein (TYROBP/DAP12) to investigate possible ligands and antibodies for modulation of CD33 signaling. Application of the CD33‑specifc antibodies P67.6 and 1c7/1 to the CD33M‑DAP12 reporter cells resulted in increased phosphorylation of the kinase SYK, which is downstream of DAP12. CD33M‑DAP12 but not CD33ΔE2‑DAP12 expressing reporter cells showed increased intracellular calcium levels upon treatment with CD33 antibody P67.6 and partially for 1c7/1. Furthermore, stimulation of human induced pluripotent stem cell‑derived microglia with the CD33 antibodies P67.6 or 1c7/1 directly counteracted the triggering receptor expressed on myeloid cells 2 (TREM2)‑induced phosphorylation of SYK and decreased the phagocytic uptake of bacterial particles. Thus, the developed reporter system confrmed CD33 pathway activation by CD33 antibody clones P67.6 and 1c7/1. -
Protein Kinases and Parkinson's Disease
International Journal of Molecular Sciences Review Protein Kinases and Parkinson’s Disease Syed Jafar Mehdi 1, Hector Rosas-Hernandez 2, Elvis Cuevas 2, Susan M. Lantz 2, Steven W. Barger 1,3, Sumit Sarkar 2, Merle G. Paule 2, Syed F. Ali 2 and Syed Z. Imam 1,2,* 1 Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; [email protected] (S.J.M.); [email protected] (S.W.B.) 2 Division of Neurotoxicology, National Center for Toxicological Research/US Food and Drug Administration, Jefferson, AR 72079, USA; [email protected] (H.R.-H.); [email protected] (E.C.); [email protected] (S.M.L.); [email protected] (S.S.); [email protected] (M.G.P.); [email protected] (S.F.A.) 3 Geriatric Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA * Correspondence: [email protected]; Tel.: +1-870-543-7989; Fax: +1-870-543-7745 Academic Editor: Katalin Prokai-Tatrai Received: 30 May 2016; Accepted: 1 September 2016; Published: 20 September 2016 Abstract: Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. -
Loss of Trem2 in Microglia Leads to Widespread Disruption of Cell Co-Expression Networks in Mouse Brain
bioRxiv preprint doi: https://doi.org/10.1101/248757; this version posted January 17, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Loss of Trem2 in microglia leads to widespread disruption of cell co-expression networks in mouse brain Guillermo Carbajosa*,1, Karim Malki2, Nathan Lawless2, Hong Wang3, John W. Ryder3, Eva Wozniak4, Kristie Wood4, Charles A. Mein4, Richard J.B. Dobson1,5,6, David A. Collier2, Michael J. O’Neill2, Angela K. Hodges7, Stephen J. Newhouse1,5,6 1. Department of Biostatistics and Health Informatics, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, United Kingdom 2. Eli Lilly and Company, Erl Wood Manor, Windlesham, United Kingdom 3. Eli Lilly and Company, Indianapolis, IN, United States of America 4. Barts and the London Genome Centre, John Vane Science Centre, Barts and the London School of Medicine and Dentistry, London, United Kingdom 5. NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, London, United Kingdom 6. Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, United Kingdom 7. Maurice Wohl Clinical Neuroscience Institute James Black Centre Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom * Corresponding author: [email protected], SGDP Centre, IoPPN, Box PO 80,De Crespigny Park, Denmark Hill, London, SE5 8AF, United Kingdom Abstract Rare heterozygous coding variants in the Triggering Receptor Expressed in Myeloid cells 2 (TREM2) gene, conferring increased risk of 1 bioRxiv preprint doi: https://doi.org/10.1101/248757; this version posted January 17, 2018. -
Parkinson's Disease Causative Mutation in Vps35 Disturbs Tetherin
cells Article Parkinson’s Disease Causative Mutation in Vps35 Disturbs Tetherin Trafficking to Cell Surfaces and Facilitates Virus Spread Yingzhuo Ding 1,†, Yan Li 1,† , Gaurav Chhetri 1 , Xiaoxin Peng 1, Jing Wu 1, Zejian Wang 1, Bo Zhao 1 , Wenjuan Zhao 1 and Xueyi Li 1,2,* 1 School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; [email protected] (Y.D.); [email protected] (Y.L.); [email protected] (G.C.); [email protected] (X.P.); [email protected] (J.W.); [email protected] (Z.W.); [email protected] (B.Z.); [email protected] (W.Z.) 2 Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA * Correspondence: [email protected] or [email protected] † These authors contributed equally to this work. Abstract: Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, characterized by progressive loss of dopaminergic neurons in the substantia nigra, intraneuronal deposition of misfolded proteins known as Lewy bodies, and chronic neuroinflammation. PD can arise from monogenic mutations, but in most cases, the etiology is unclear. Viral infection is gaining increasing attentions as a trigger of PD. In this study, we investigated whether the PD-causative Citation: Ding, Y.; Li, Y.; Chhetri, G.; 620 aspartate (D) to asparagine (N) mutation in the vacuolar protein sorting 35 ortholog (Vps35) Peng, X.; Wu, J.; Wang, Z.; Zhao, B.; precipitated herpes simplex virus (HSV) infection. We observed that ectopic expression of Vps35 Zhao, W.; Li, X. Parkinson’s Disease significantly reduced the proliferation and release of HSV-1 virions; the D620N mutation rendered Causative Mutation in Vps35 Vps35 a partial loss of such inhibitory effects.