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Progranulin

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https://www.readbyqxmd.com/read/28100408/increased-cerebrospinal-fluid-progranulin-correlates-with-interleukin-6-in-the-acute-phase-of-neuromyelitis-optica-spectrum-disorder
#1
Akio Kimura, Masao Takemura, Kuniaki Saito, Ginette Serrero, Nobuaki Yoshikura, Yuichi Hayashi, Takashi Inuzuka
We examined progranulin (PGRN) levels in cerebrospinal fluid (CSF) samples during the acute phase in 15 patients with neuromyelitis optica spectrum disorders (NMOSD) and compared the results with those from 17 patients with multiple sclerosis (MS), 30 patients with other inflammatory neurological diseases (OIND), and 20 non-inflammatory controls (NIC). CSF PGRN levels of NMOSD patients were significantly higher than those of MS patients and NICs. These levels correlated with CSF interleukin-6 levels, CSF cell counts, CSF protein levels, improvements in the Expanded Disability Status Scale score, and affected total spinal cord lesion length in the NMOSD patients...
January 12, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28073925/progranulin-regulates-lysosomal-function-and-biogenesis-through-acidification-of-lysosomes
#2
Yoshinori Tanaka, Genjiro Suzuki, Takashi Matsuwaki, Masato Hosokawa, Geidy Serrano, Thomas G Beach, Keitaro Yamanouchi, Masato Hasegawa, Masugi Nishihara
Progranulin (PGRN) haploinsufficiency resulting from loss-of-function mutations in the PGRN gene causes frontotemporal lobar degeneration accompanied by TDP-43 accumulation, and patients with homozygous mutations in the PGRN gene present with neuronal ceroid lipofuscinosis. Although it remains unknown why PGRN deficiency causes neurodegenerative diseases, there is increasing evidence that PGRN is implicated in lysosomal functions. Here, we show PGRN is a secretory lysosomal protein that regulates lysosomal function and biogenesis by controlling the acidification of lysosomes...
January 10, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28073702/serum-progranulin-as-an-indicator-of-neutrophilic-airway-inflammation-and-asthma-severity
#3
So Young Park, Gyong Hwa Hong, Sunjoo Park, Bomi Shin, Sun-Young Yoon, Hyouk-Soo Kwon, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho
BACKGROUND: Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. OBJECTIVE: To investigate the association between serum progranulin levels and various clinical features in patients with asthma. METHODS: Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected...
December 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#4
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28069809/the-receptor-interacting-serine-threonine-protein-kinase-1-ripk1-regulates-progranulin-levels
#5
Amanda R Mason, Lisa P Elia, Steven Finkbeiner
Progranulin (PGRN), a secreted growth factor, is a key regulator of inflammation and is genetically linked to two common and devastating neurodegenerative diseases. Haploinsufficiency mutations in GRN, the gene encoding PGRN, cause frontotemporal dementia (FTD) and a GRN SNP confers significantly increased risk for Alzheimer's disease (AD). Because cellular and animal data indicate that increasing PGRN can reverse phenotypes of both FTD and AD, modulating PGRN level has been proposed as a therapeutic strategy for both diseases...
January 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28011648/foxo4-and-stat3-dependent-il-10-production-by-progranulin-in-regulatory-t-cells-restrains-inflammatory-arthritis
#6
Wenyu Fu, Wenhuo Hu, Lei Shi, Jyoti Joshi Mundra, GuoZhi Xiao, Michael L Dustin, Chuan-Ju Liu
Progranulin (PGRN) restrains inflammation and is therapeutic against inflammatory arthritis; however, the underlying immunological mechanism remains unknown. In this study, we demonstrated that anti-inflammatory cytokine IL-10 was a critical mediator for PGRN-mediated anti-inflammation in collagen-induced arthritis by using PGRN and IL-10 genetically modified mouse models. IL-10 green fluorescent protein reporter mice revealed that regulatory T (Treg) cells were the predominant source of IL-10 in response to PGRN...
December 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28002034/serum-progranulin-levels-in-type-2-diabetic-patients-with-metabolic-syndrome
#7
Azam Shafaei, Abdoljalal Marjani, Masoud Khoshnia
INTRODUCTION: The role of progranulin in individuals with metabolic syndrome is not exactly clear.We aimed to assess the serum level of progranulin in type 2 diabetic patients with and without metabolic syndrome and compare them with healthy controls. METHODS: The study included 60 patients with type 2 diabetes and 30 healthy individuals as control groups. Biochemical parameters and progranulin levels were determined. RESULTS: Subjects with metabolic syndrome showed significantly higher levels of triglyceride, waist circumference, BMI, systolic and diastolic blood pressure than subjects without metabolic syndrome and the control groups, while HDL-cholesterol level was significantly lower in subjects with metabolic syndrome...
December 1, 2016: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
https://www.readbyqxmd.com/read/27997711/alzheimer-neuropathology-without-frontotemporal-lobar-degeneration-hallmarks-tar-dna-binding-protein-43-inclusions-in-missense-progranulin-mutation-cys139arg
#8
Veronica Redaelli, Giacomina Rossi, Emanuela Maderna, Gabor G Kovacs, Elena Piccoli, Paola Caroppo, Francesca Cacciatore, Sonia Spinello, Marina Grisoli, Giuliano Sozzi, Andrea Salmaggi, Fabrizio Tagliavini, Giorgio Giaccone
Null mutations in progranulin gene (GRN) reduce the progranulin production resulting in haploinsufficiency and are tightly associated with tau-negative frontotemporal lobar degeneration with TAR DNA-binding protein 43-positive inclusions (FTLD-TDP). Missense mutations of GRN were also identified, but their effects are not completely clear, in particular unanswered is the question of what neuropathology they elicit, also considering that their occurrence has been reported in patients with typical clinical features of Alzheimer disease...
December 20, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27980241/therapeutic-strategies-to-attenuate-hemorrhagic-transformation-after-tissue-plasminogen-activator-treatment-for-acute-ischemic-stroke
#9
Masato Kanazawa, Tetsuya Takahashi, Masatoyo Nishizawa, Takayoshi Shimohata
This review focuses on the mechanisms and emerging concepts of stroke and therapeutic strategies for attenuating hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) treatment for acute ischemic stroke (AIS). The therapeutic time window for tPA treatment has been extended. However, the patients who are eligible for tPA treatment are still <5% of all patients with AIS. The risk of serious or fatal symptomatic hemorrhage increases with delayed initiation of treatment. HT is thought to be caused by 1) ischemia/reperfusion injury; 2) the toxicity of tPA itself; 3) inflammation; and/or 4) remodeling factor-mediated effects...
December 13, 2016: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/27941174/nocturnal-levels-of-chemerin-and-progranulin-in-adolescents-influence-of-sex-body-mass-index-glucose-metabolism-and-sleep
#10
Johann Daxer, Theresa Herttrich, Ying Y Zhao, Mandy Vogel, Andreas Hiemisch, Kathrin Scheuermann, Antje Körner, Jürgen Kratzsch, Wieland Kiess, Mirja Quante
BACKGROUND: Adipokines have been implicated in obesity, insulin resistance and sleep regulation. However, the role of chemerin and progranulin, two recently described adipokines, in the context of sleep remains unclear. The aim of this study was to compare nocturnal serum chemerin and progranulin levels between overweight/obese and normal-weight adolescents and to assess variations by sex, across different sleep stages and in relation to glucose metabolism. METHODS: The study sample included 34 overweight/obese and 32 normal-weight adolescents from secondary schools and the Leipzig Research Center for Civilization Diseases (LIFE) Child study cohort...
January 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/27921079/data-file-of-a-deep-proteome-analysis-of-the-prefrontal-cortex-in-aged-mice-with-progranulin-deficiency-or-neuronal-overexpression-of-progranulin
#11
Juliana Heidler, Stefanie Hardt, Ilka Wittig, Irmgard Tegeder
Progranulin deficiency is associated with neurodegeneration in humans and in mice. The mechanisms likely involve progranulin-promoted removal of protein waste via autophagy. We performed a deep proteomic screen of the pre-frontal cortex in aged (13-15 months) female progranulin-deficient mice (GRN(-/-)) and mice with inducible neuron-specific overexpression of progranulin (SLICK-GRN-OE) versus the respective control mice. Proteins were extracted and analyzed per liquid chromatography/mass spectrometry (LC/MS) on a Thermo Scientific™ Q Exactive Plus equipped with an ultra-high performance liquid chromatography unit and a Nanospray Flex Ion-Source...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27921076/yeast-2-hybrid-data-file-showing-progranulin-interactions-in-human-fetal-brain-and-bone-marrow-libraries
#12
Irmgard Tegeder
Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27903608/progranulin-and-the-receptor-tyrosine-kinase-epha2-partners-in-crime
#13
Babykumari Chitramuthu, Andrew Bateman
Progranulin is a secreted protein with roles in tumorigenesis, inflammation, and neurobiology, but its signaling receptors have remained unclear. In this issue, Neill et al. (2016. J. Cell Biol https://doi.org/10.1083/jcb.201603079) identify the tyrosine kinase EphA2 as a strong candidate for such a receptor, providing insight into progranulin and EphA2 signaling.
December 5, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27903606/epha2-is-a-functional-receptor-for-the-growth-factor-progranulin
#14
Thomas Neill, Simone Buraschi, Atul Goyal, Catherine Sharpe, Elizabeth Natkanski, Liliana Schaefer, Andrea Morrione, Renato V Iozzo
Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis...
December 5, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27872232/therapeutic-potential-of-progranulin-in-hyperhomocysteinemia-induced-cardiorenal-dysfunction
#15
Yi Fu, Yu Sun, Meng Zhou, Xiaojie Wang, Ziying Wang, Xinbing Wei, Yan Zhang, Zeyu Su, Kaili Liang, Wei Tang, Fan Yi
Hyperhomocysteinemia (hHcys) is an important independent risk factor for the development of cardiovascular disease and end-stage renal disease. Although multiple approaches lowering the levels of homocysteine have been used in experimental studies and clinical trials, there is no effective therapy available to fully prevent homocysteine-induced injury. Therefore, identifying key molecules in the pathogenic pathways may provide clues to develop new therapeutic strategies for the treatment of hHcys-associated injury beyond lowering the plasma homocysteine levels...
November 21, 2016: Hypertension
https://www.readbyqxmd.com/read/27845584/immune-modulation-in-sepsis-is-there-a-place-for-progranulin
#16
Haibo Zhang, Yimin Li, Tom van der Poll
No abstract text is available yet for this article.
November 15, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27844039/increased-prevalence-of-autoimmune-disease-within-c9-and-ftd-mnd-cohorts-completing-the-picture
#17
Zachary A Miller, Virginia E Sturm, Gamze Balci Camsari, Anna Karydas, Jennifer S Yokoyama, Lea T Grinberg, Adam L Boxer, Howard J Rosen, Katherine P Rankin, Maria Luisa Gorno-Tempini, Giovanni Coppola, Daniel H Geschwind, Rosa Rademakers, William W Seeley, Neill R Graff-Radford, Bruce L Miller
OBJECTIVE: To determine the prevalence of autoimmune disease in symptomatic C9ORF72 (C9) mutation carriers and frontotemporal dementia with motor neuron disease (FTD/MND) cohorts. METHODS: In this case-control study, we reviewed the clinical histories of 66 patients with FTD/MND and 57 symptomatic C9 carriers (24 overlapping cases), a total of 99 charts, for history of autoimmune disease. The prevalence of autoimmune disease in C9 and FTD/MND cohorts was determined by χ(2) and Fisher exact comparisons between the combined C9 and FTD/MND group with normal control, Alzheimer disease, and progressive supranuclear palsy cohorts, as well as comparisons within C9 and FTD/MND cohorts...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27836396/progranulin-as-a-novel-factor-in-gaucher-disease
#18
Francis Y M Choy, Chloe L Christensen
No abstract text is available yet for this article.
November 2016: EBioMedicine
https://www.readbyqxmd.com/read/27830341/serum-progranulin-levels-in-hispanic-rheumatoid-arthritis-patients-treated-with-tnf-antagonists-a-prospective-observational-study
#19
Jennifer Johnson, Karen Yeter, Rosy Rajbhandary, Rebekah Neal, Qingyun Tian, Jinlong Jian, Natalie Fadle, Lorenz Thurner, Chuanju Liu, William Stohl
Since progranulin (PGRN) is a natural ligand of TNF receptors, we assessed whether serum PGRN levels predict and/or reflect responsiveness of RA patients to TNF-antagonist therapy. TNF-antagonist-naïve RA patients (N = 35) were started on TNF-antagonist therapy. At baseline and at follow-up visits, DAS28-ESR, DAS28-CRP, and CDAI were calculated, and venous blood was collected for serum PGRN determination. Disease activity and clinical response were based on EULAR criteria. Baseline serum PGRN levels varied considerably and correlated with ESR and CRP...
November 9, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27819158/diagnostic-and-prognostic-significance-of-neurofilament-light-chain-nf-l-but-not-progranulin-and-s100b-in-the-course-of-amyotrophic-lateral-sclerosis-data-from-the-german-mnd-net
#20
Petra Steinacker, André Huss, Benjamin Mayer, Torsten Grehl, Julian Grosskreutz, Guntram Borck, Jens Kuhle, Dorothée Lulé, Thomas Meyer, Patrick Oeckl, Susanne Petri, Jochen Weishaupt, Albert C Ludolph, Markus Otto
There is a need for diagnostic, prognostic, and monitoring blood biomarkers for ALS. We aimed to analyse and compare proposed candidate markers for disease progression in the course of ALS. Blood samples were taken from 125 ALS patients, including nine patients with C9orf72 or SOD1 mutation, at regular intervals of six months. ALS patients were characterized by the ALS functional rating scale (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). We quantified neurofilament light chain (NF-L), S100B, and progranulin (PGRN) and analysed it in relation to disease progression...
November 5, 2016: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
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