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Progranulin

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https://www.readbyqxmd.com/read/28225367/progranulin-gene-variation-affects-serum-progranulin-levels-differently-in-danish-bipolar-individuals-compared-with-healthy-controls
#1
Henriette N Buttenschøn, Marit N Nielsen, Gangadaar Thotakura, Chris W Lee, Anders Nykjær, Ole Mors, Simon Glerup
OBJECTIVES: The identification of peripheral biomarkers for bipolar disorder is of great importance and has the potential to improve diagnosis, treatment and prognosis. Recent studies have reported lower plasma progranulin levels in bipolar individuals compared with controls and association with single nucleotide polymorphisms (SNPs) within the progranulin gene (GRN). In the present study, we investigated the effect of GRN and sortilin (SORT1) gene variation on serum progranulin levels in bipolar individuals and controls...
February 20, 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/28194047/progranulin-inhibits-human-t-lymphocyte-proliferation-by-inducing-the-formation-of-regulatory-t-lymphocytes
#2
Kyu Hwan Kwack, Hyeon-Woo Lee
We have examined the effect of progranulin (PGRN) on human T cell proliferation and its underlying mechanism. We show that PGRN inhibits the PHA-induced multiplication of T lymphocytes. It increases the number of iTregs when T lymphocytes are activated by PHA but does not do so in the absence of PHA. PGRN-mediated inhibition of T lymphocyte proliferation, as well as the induction of iTregs, was completely reversed by a TGF-β inhibitor or a Treg inhibitor. PGRN induced TGF-β secretion in the presence of PHA whereas it did not in the absence of PHA...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28174682/glucose-deprivation-regulates-the-progranulin-sortilin-axis-in-pc12-cells
#3
Ken-Ichi Kawashima, Yuri Ishiuchi, Miki Konnai, Saori Komatsu, Hitoshi Sato, Hideo Kawaguchi, Nobumitsu Miyanishi, Jérôme Lamartine, Masugi Nishihara, Taku Nedachi
Progranulin (PGRN) is a growth factor implicated in several neurodegenerative diseases, such as frontotemporal lobar degeneration. Despite its important role in the central nervous system (CNS), the mechanisms controlling PGRN expression in the CNS are largely unknown. Recent evidence, however, suggested that several stressors, such as hypoxia, acidosis, or oxidative stress, induce PGRN expression. The present study was mainly aimed at determining whether and, if so, how glucose deprivation affects PGRN expression in PC12 cells...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28153380/grn-deletion-in-familial-frontotemporal-dementia-showing-association-with-clinical-variability-in-3-familial-cases
#4
Graziella Milan, Sabrina Napoletano, Sabina Pappatà, Maria Teresa Gentile, Luca Colucci-D'Amato, Gennaro Della Rocca, Anna Maciag, Carmen Palermo Rossetti, Laura Fucci, Annibale Puca, Dario Grossi, Alfredo Postiglione, Emilia Vitale
Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns. We present evidence that all the available patients in these 3 familial cases are carrying the rare GRN gene exon 6 deletion g10325_10331delCTGCTGT (relative to nt 1 inNG_007886...
January 9, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28143512/progranulin-causes-adipose-insulin-resistance-via-increased-autophagy-resulting-from-activated-oxidative-stress-and-endoplasmic-reticulum-stress
#5
Qinyue Guo, Lin Xu, Huixia Li, Hongzhi Sun, Jiali Liu, Shufang Wu, Bo Zhou
BACKGROUND: Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. METHODS: In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed...
January 31, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28127696/angiogenin-prevents-progranulin-a9d-mutation-induced-neuronal-like-cell-apoptosis-through-cleaving-trnas-into-tirnas
#6
Siqi Li, Yongdui Chen, Desen Sun, Rongpai Bai, Xiangwei Gao, Yi Yang, Jinghao Sheng, Zhengping Xu
Gene defects have been recognized as prominent factors in the etiology and pathogenesis of neurodegeneration. Among 60 neurodegeneration-related mutations in progranulin (PGRN), a mutation in PGRN gene exon 1 introduces a charged amino acid in the hydrophobic core of its signal peptide at residue 9 (named PGRN A9D) and results in incorrect cytoplasmic sorting. However, the pathogenesis of this mutation remains elusive. To address this issue, we first examined the subcellular distribution of PGRN A9D in human neuronal-like cells (SH-SY5Y)...
January 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28126008/elevated-tmem106b-levels-exaggerate-lipofuscin-accumulation-and-lysosomal-dysfunction-in-aged-mice-with-progranulin-deficiency
#7
Xiaolai Zhou, Lirong Sun, Owen Adam Brady, Kira A Murphy, Fenghua Hu
Mutations resulting in haploinsufficiency of progranulin (PGRN) cause frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a devastating neurodegenerative disease. Accumulating evidence suggest a crucial role of progranulin in maintaining proper lysosomal function during aging. TMEM106B has been identified as a risk factor for frontotemporal lobar degeneration with progranulin mutations and elevated mRNA and protein levels of TMEM106B are associated with increased risk for frontotemporal lobar degeneration...
January 26, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28120721/progranulin-a-new-adipokine-at-the-crossroads-of-metabolic-syndrome-diabetes-dyslipidemia-and-hypertension
#8
Agnieszka Korolczuk, Jerzy Bełtowski
BACKGROUND: Progranulin is a multifunctional regulatory protein with growth-promoting, neuroprotective and antiinflammatory activities. Recent studies indicate that progranulin is one of the adipose tissue hormones (adipokines). Progranulin expression in visceral adipose tissue and circulating progranulin concentration are increased in obesity and hyperprogranulinemia is involved in the pathogenesis of obesity-associated insulin resistance. Progranulin impairs insulin signaling and reduces insulin-induced glucose uptake both in vitro and in vivo whereas progranulin deficiency protects from high fat diet-induced insulin resistance...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28100408/increased-cerebrospinal-fluid-progranulin-correlates-with-interleukin-6-in-the-acute-phase-of-neuromyelitis-optica-spectrum-disorder
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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