R&D Systems Tools for Cell Biology Research™ R&D Systems Products for Neuroscience Research ON THE COVER This illustration was featured in the Cytokine Bulletin (2010, Issue 1). TLR2 IL-6 IL-6 R MOG IL-21 R TGF-β R STAT3 Dendritic TGF-β Cell STAT3 Batf, RORγt IL-23 Batf RORγt Th17 Cell IL-23 R IL-17 JunB Batf RORγt IL-17 NO Myelin TNF-α Axon MMPs Macrophages Neuron Oligodendrocyte Prolonged production of IL-17 by Th17 cells is dependent on the transcription factor Batf. Recent studies suggest that prolonged production of IL-17 by Th17 cells is dependent on the synergistic actions of the RORt and Batf-JunB transcription factors. These fi ndings may have implications for Th17-related autoimmune disorders such as multiple sclerosis. Following induction of autoimmune conditions in mice using myelin oligodendrocyte glycoprotein (MOG) immunization, diff erentiated Th17 cells secrete proinfl ammatory cytokines, and activated macrophages destroy myelin and damage oligodendrocytes. It remains to be determined whether the induction of Batf expression is dependent on STAT3 in Th17 cells, and whether an interaction between Batf and Irf4 or Ahr is required to promote the respective induction of IL-21 and IL-22. Schraml, B.U. et al. (2009) Nature 460:405. To request the most recent issue of the Cytokine Bulletin and other R&D Systems literature please visit www.RnDSystems.com/go/Request R&D Systems Tools for Cell Biology Research™ R&D Systems Cytokine Bulletin Cytokine BULLETIN 2011 | Issue 2 Adipose Tissue INSIDE s)NFLAMMATION s$ECREASEDADIPOGENESIS IL-1E PAGE 2 s2EDUCEDADIPOCYTEMETABOLICACTIVITY Synaptic EphB2-NMDA Receptor s)NSULIN2ESISTANCE Dynamics: A New Hope for Alzheimer’s Disease Obesity-related Adipocyte Danger Signal PAGE 3 CXCR4: A Receptor Macrophage ROS for Extracellular Ubiquitin Pro-IL-1E PAGE 4 Nlrp3 TSLP, Inflammation, & Cancer PAGE 5 Pancreas Caspase-1 Mature IL-1E RECENT CITATIONS: R&D Systems Products for TGF-E ASC Research IsletIslet ofof LangerhansLangerhans Pro-Caspase-1 PAGE 6-7 TECHNICAL NOTE & MEETINGS: something PAGE 8 IL-1E s)MPAIREDPANCREATICE cell function NEW TOOLS: sE cell death Custom Premix Fluorokine® Multianalyte Profiling Kits Obesity-Induced Inflammasome Activation in Key Metabolic Tissues Promotes Chronic Inflammation and Insulin Resistance. Obesity-related danger signals, such as palmitate, & VersaMAP™ Development System ceramide, high glucose concentrations, islet amyloid polypeptide, defective autophagy, or mitochondrial dysfunction may lead to the generation of reactive oxygen species (ROS) and subsequent activation of the Nlrp3 inflammasome in adipocytes, pancreatic islet cells, or infiltrating macrophages present in these tissues. Nlrp3 inflammasome activation promotes the cleavage and activation of Caspase-1, resulting in the secretion of IL-1E, a proinflammatory cytokine that negatively affects adipocyte differentiation, inhibits insulin signaling, and has BIObrief Mini Poster a cytotoxic effect on insulin-producing pancreaticE cells. Identification of a connection between obesity, the inflammasome, and insulin resistance links inflammasome activation with The Double Life of TGF-E: metabolic tissue dysfunction, which may contribute to the pathogenesis of type II diabetes, and potentially other diseases associated with obesity-induced inflammation. A Tumor Suppressing & Tumor Obesity-induced Activation of the Nlrp3 Inflammasome Promoting Factor Promotes Insulin Resistance Obesity is a serious health problem characterized by an excessive expansion of the white adipose tissue coupled with a state of chronic, low-grade inflammation.1 Inflammation occurs as a result of immune cell infiltration of the adipose tissue and increased production of pro-inflammatory cytokines.2 These changes www. RnDSystems.com negatively affect normal adipocyte functions, such as triglyceride storage and lipolysis, leading to high circulating levels of free fatty acids and ectopic lipid accumulation.3 In addition, elevated levels of pro- inflammatory cytokines, including IL-1E, IL-6, and TNF-D, reduce insulin sensitivity, which can lead to the development of type II diabetes if insulin production by the pancreatic E cells is not sufficiently increased.4-6 Although it has been recognized for some time that pro-inflammatory factors inhibit insulin signaling, the molecular mechanisms that trigger inflammation and sustained cytokine production during obesity are not well understood. The first evidence of an obesity-related signal that could initiate the inflammatory response came from reports that saturated fatty acids activate Toll-like receptors (TLRs).7-9 TLRs are a family of membrane- associated pattern recognition receptors that detect invading pathogens and activate the innate immune response. These studies demonstrated that fatty acids, like microbial pathogens, promote TLR-induced inflammation. It was subsequently shown that disruption of TLR4 or a loss of function mutation in TLR4 protects against high fat diet-induced insulin resistance in mice, suggesting that fatty acid-induced TLR4 signaling provides a link between obesity, inflammation, and insulin resistance.10,11 Continued on page 7 TABLE OF CONTENTS R&D SYSTEMS NEUROSCIENCE CATALOG The fi eld of neuroscience is one of the most fascinating and complex branches of biological science. At the earliest stages of development, the regulated expression and activity of specifi c genes directs multipotent stem cells down neural pathways. Morphogenic factors regulate neuroectoderm diff erentiation, the formation of the neural tube, and fi nally the development of the brain and spinal cord. The growth cones at the tips of extending axons are exquisitely sensitive to a myriad of environmental cues that govern their directed migration toward specifi c targets. Once there, the process of synaptogenesis incorporates neurons into complex electrochemical networks. By adulthood, the brain may contain more than 100 trillion synapses, their integrated signals controlling virtually all aspects of life. With age, the nervous system becomes more vulnerable to dysfunction and disease. For instance, the risk of Alzheimer's disease doubles every 5 years after the age of 65 and reaches 50% by the age of 85. We advance our understanding of nervous system pathology with the hope of developing therapies to address some of society's most economically and socially devastating diseases. R&D Systems off ers a range of high quality reagents for studying all areas of neuroscience, from neural stem cells to neurodegenerative disease. These include a wide range of high performance antibodies, and the most referenced collection of bioactive proteins and immunoassays in the industry. Primary rat and mouse cortical stem cells are also available, as well as kits for the expansion, diff erentiation, and identifi cation of neural stem cells, and multiplex assays for the simultaneous detection of multiple analytes. NEUROSCIENCE-RELATED MOLECULE FAMILIES NEUROTROPHIC FACTORS & RECEPTORS . 2-9 NEURAL STEM CELLS . 36-43 GDNF Family Ligands & Receptors . 2-3 Neural Stem Cells & Diff erentiation Markers . 36-41 Neurotrophin Family Ligands & Receptors . 4-5 Adult Neurogenesis . 42-43 VPS10P-domain Receptor Family . 6-7 SYNAPTIC PROTEINS & NEUROTRANSMITTERS . 44-49 Additional Neurotrophic Factors & Receptors . 8-9 Synaptic Proteins . 44-47 NEURAL DEVELOPMENT & AXON GUIDANCE . 10-29 Neurotransmitters, Receptors, & Related Molecules . 48-49 Ephrin Ligands & Eph Receptors . 10-11 NEURODEGENERATIVE DISEASES . 50-86 Hedgehog Family . 12-13 Alzheimer’s Disease & APP Metabolism . 50-51 Netrin Family . 14-15 Parkinson’s Disease . 52-53 Semaphorins, Plexins, & Related Molecules . 16-17 Amyotrophic Lateral Sclerosis . 54-55 Slit Ligands & ROBO Receptors . 18-19 Multiple Sclerosis . 56-57 Wnt Ligands, Frizzled Receptors, & Related Molecules . 20-23 Diabetic Peripheral Neuropathy . 58-59 Nogo Proteins & Receptors . 24-25 Neuroinfl ammation . 60-61 Bone Morphogenetic Proteins & Receptors . 26-27 Autophagy & the Ubiquitin Proteasome System . 62-65 Repulsive Guidance Molecules & Receptors . 28-29 Apoptosis . 66-73 Additional Axon Guidance Molecules . 29 SIGNAL TRANSDUCTION . 74-86 CELL ADHESION MOLECULES FOR NEUROSCIENCE . 30-35 SPECIALIZED TOOLS FOR NEUROSCIENCE RESEARCH . 87-105 Contactin Family. 30-31 Antibody Arrays & Multiplex Assays . 87-94 Nectins & Cadherins. 32-33 Neural Stem Cell Culture Media & Kits . 94-97 SynCAM, NCAM, & L1CAM Families . 34-35 Neuronal Cell Culture Products . 97-98 Flow Cytometry, Western Blotting, & Cell/Tissue Staining . 99-104 Chromatin IP Kits & Modules . 105 NOTES . 106-108 For more information visit our website at www.RnDSystems.com/go/Neuroscience NEUROTROPHIC FACTORS & RECEPTORS GDNF Family Ligands & Receptors Following its original purifi cation from a rat glioma cell line supernatant, Although GFR is linked to the plasma membrane at lipid rafts by a glial cell line-derived neurotrophic factor (GDNF) was identifi ed as a glycosylphosphatidylinositol (GPI) anchor, cleavage by proteases or survival factor for dopaminergic neurons in the midbrain.1 Subsequent phospholipases generates a soluble form of the receptor that can exert studies have shown that GDNF is critical for the proliferation, migration, distant actions. 2,3 and diff erentiation of several neuronal populations. In addition, GDNF Many groups have studied GDNF as a potential therapeutic agent for the exerts important biological eff ects outside the central nervous system, treatment of Parkinson’s disease (PD), a condition