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Progranulin

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https://www.readbyqxmd.com/read/27903608/progranulin-and-the-receptor-tyrosine-kinase-epha2-partners-in-crime
#1
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.
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27903606/epha2-is-a-functional-receptor-for-the-growth-factor-progranulin
#2
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...
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27872232/therapeutic-potential-of-progranulin-in-hyperhomocysteinemia-induced-cardiorenal-dysfunction
#3
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
#4
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
#5
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
#6
Francis Y M Choy, Chloe L Christensen
No abstract text is available yet for this article.
November 5, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27830341/serum-progranulin-levels-in-hispanic-rheumatoid-arthritis-patients-treated-with-tnf-antagonists-a-prospective-observational-study
#7
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
#8
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
https://www.readbyqxmd.com/read/27814992/a-cluster-of-progranulin-c157kfsx97-mutations-in-southern-italy-clinical-characterization-and-genetic-correlations
#9
Cinzia Coppola, Dario Saracino, Gianfranco Puoti, Giacomo Lus, Clemente Dato, Isabelle Le Ber, Jeremie Pariente, Paola Caroppo, Elena Piccoli, Fabrizio Tagliavini, Giuseppe Di Iorio, Giacomina Rossi
Frontotemporal lobar degeneration (FTLD) is a group of neurodegenerative diseases displaying high clinical, pathologic, and genetic heterogeneity. Several autosomal dominant progranulin (GRN) mutations have been reported, accounting for 5%-10% of FTLD cases worldwide. In this study, we described the clinical characteristics of 7 Italian patients, 5 with a diagnosis of frontotemporal dementia behavioral variant and 2 of corticobasal syndrome (CBS), carrying the GRN deletion g.101349_101355delCTGCTGT, resulting in the C157KfsX97 null mutation, and hypothesized the existence of a founder effect by means of haplotype sharing analysis...
October 11, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27789271/progranulin-recruits-hsp70-to-%C3%AE-glucocerebrosidase-and-is-therapeutic-against-gaucher-disease
#10
Jinlong Jian, Qing-Yun Tian, Aubryanna Hettinghouse, Shuai Zhao, Helen Liu, Jianlu Wei, Gabriele Grunig, Wujuan Zhang, Kenneth D R Setchell, Ying Sun, Herman S Overkleeft, Gerald L Chan, Chuan-Ju Liu
Gaucher disease (GD), the most common lysosomal storage disease, is caused by mutations in GBA1 encoding of β-glucocerebrosidase (GCase). Recently it was reported that progranulin (PGRN) insufficiency and deficiency associated with GD in human and mice, respectively. However the underlying mechanisms remain unknown. Here we report that PGRN binds directly to GCase and its deficiency results in aggregation of GCase and its receptor LIMP2. Mass spectrometry approaches identified HSP70 as a GCase/LIMP2 complex-associated protein upon stress, with PGRN as an indispensable adaptor...
October 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27778404/progranulin-protects-against-exaggerated-axonal-injury-and-astrogliosis-following-traumatic-brain-injury
#11
Lutz Menzel, Lisa Kleber, Carina Friedrich, Regina Hummel, Larissa Dangel, Jennifer Winter, Katja Schmitz, Irmgard Tegeder, Michael K E Schäfer
In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn(-/-) ) 24 h and 5 days after experimental TBI...
October 25, 2016: Glia
https://www.readbyqxmd.com/read/27776152/serum-and-urinary-progranulin-in-diabetic-kidney-disease
#12
Bruna Bellincanta Nicoletto, Thaiana Cirino Krolikowski, Daisy Crispim, Luis Henrique Canani
Progranulin has been recognized as an adipokine related to obesity, insulin resistance and type 2 diabetes mellitus (T2DM). There are scarce data regarding progranulin and kidney disease, but there are some data linking diabetic kidney disease (DKD) and increased progranulin levels. We aimed to better describe the relationship between serum and urinary progranulin levels and DKD in T2DM. This is a case-control study including four groups of subjects: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1...
2016: PloS One
https://www.readbyqxmd.com/read/27770818/progranulin-promotes-peripheral-nerve-regeneration-and-reinnervation-role-of-notch-signaling
#13
Christine Altmann, Verica Vasic, Stefanie Hardt, Juliana Heidler, Annett Häussler, Ilka Wittig, Mirko H H Schmidt, Irmgard Tegeder
BACKGROUND: Peripheral nerve injury is a frequent cause of lasting motor deficits and chronic pain. Although peripheral nerves are capable of regrowth they often fail to re-innervate target tissues. RESULTS: Using newly generated transgenic mice with inducible neuronal progranulin overexpression we show that progranulin accelerates axonal regrowth, restoration of neuromuscular synapses and recovery of sensory and motor functions after injury of the sciatic nerve...
October 22, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27767988/a-novel-loss-of-function-grn-mutation-p-tyr229-%C3%A2-clinical-and-neuropathological-features
#14
Liina Kuuluvainen, Minna Pöyhönen, Petra Pasanen, Maija Siitonen, Jaana Rummukainen, Pentti J Tienari, Anders Paetau, Liisa Myllykangas
Mutations in the progranulin (GRN) gene represent about 5-10% of frontotemporal lobar degeneration (FTLD). We describe a proband with a novel GRN mutation c.687T>A, p.(Tyr229*), presenting with dyspraxia, dysgraphia, and dysphasia at the age of 60 and a very severe FTLD neuropathological phenotype with TDP43 inclusions. The nephew of the proband had signs of dementia and personality changes at the age of 60 and showed similar but milder FTLD pathology. Three other family members had had early-onset dementia...
October 20, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27760429/cerebrospinal-fluid-progranulin-but-not-serum-progranulin-is-reduced-in-grn-negative-frontotemporal-dementia
#15
Carlo Wilke, Frank Gillardon, Christian Deuschle, Markus A Hobert, Iris E Jansen, Florian G Metzger, Peter Heutink, Thomas Gasser, Walter Maetzler, Cornelis Blauwendraat, Matthis Synofzik
BACKGROUND AND OBJECTIVE: Reduced progranulin levels are a hallmark of frontotemporal dementia (FTD) caused by loss-of-function (LoF) mutations in the progranulin gene (GRN). However, alterations of central nervous progranulin expression also occur in neurodegenerative disorders unrelated to GRN mutations, such as Alzheimer's disease. We hypothesised that central nervous progranulin levels are also reduced in GRN-negative FTD. METHODS: Progranulin levels were determined in both cerebrospinal fluid (CSF) and serum in 75 subjects (37 FTD patients and 38 controls)...
October 20, 2016: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/27744566/progranulin-as-a-predictive-factor-of-response-to-chemotherapy-in-advanced-biliary-tract-carcinoma
#16
Jong-Ho Kim, In-Gu Do, Kyungeun Kim, Jin Hee Sohn, Hong Joo Kim, Woo Kyu Jeon, Sung Ryol Lee, Byung Ho Son, Jun Ho Shin, Heerim Nam, Heon-Ju Kwon, Mi Sung Kim, Hyun Pyo Hong, Ginette Serrero, Dong-Hoe Koo
PURPOSE: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the proliferation and survival of several cancer cell types. However, little is known about the prognostic role of PGRN in advanced biliary tract cancers (BTCs). METHODS: A retrospective analysis was performed on patients with advanced BTC who received palliative chemotherapy between July 2004 and November 2014. PGRN expression was immunohistochemically evaluated according to staining intensity of tumor and peritumoral cells...
October 15, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27706709/growth-factor-progranulin-blocks-tumor-necrosis-factor-%C3%AE-mediated-inhibition-of-osteoblast-differentiation
#17
N Wang, J Zhang, J X Yang
Tumor necrosis factor-α (TNF-α) stimulates osteoclast differentiation and suppresses osteoblast differentiation, leading to bone loss and decreased bone mass in local inflammation areas in patients with rheumatoid arthritis. The growth factor progranulin (PGRN) is expressed in various types of cells and play crucial roles in the pathogenesis of atherosclerosis and arthritis by blocking TNF-α. Here, we investigated the role of PGRN in blocking TNF-α-mediated inhibition of osteoblast differentiation and the regulatory mechanism...
September 9, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27703466/progranulin-levels-in-plasma-and-cerebrospinal-fluid-in-granulin-mutation-carriers
#18
Lieke H H Meeter, Holger Patzke, Gordon Loewen, Elise G P Dopper, Yolande A L Pijnenburg, Rick van Minkelen, John C van Swieten
BACKGROUND: Pathogenic mutations in the granulin gene (GRN) are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels. METHODS: Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls...
May 2016: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/27693922/biological-function-analysis-of-monoclonal-antibodies-against-human-granulins-in%C3%A2-vitro-using-u251-cells-as-a-model
#19
Yanqing Li, Ya Li, Mingfu Ye, Dongyang Wang, Junli Zhao, Xiaohong Sun, Qinwen Mao, Haibin Xia
Progranulin (PGRN), a highly glycosylated, secreted 593 amino acid precursor protein, is a multifunctional molecule that is critical for early embryogenesis, wound repair, inflammatory and tumorigenesis. PGRN can be proteolytically cleaved into seven cysteine-rich granulin (Grn) peptides: G, F, B, A, C, D and E. Both PGRN and its constituent Grn peptides have been implicated in a wide variety of biological activities. However, their functions are far from clear, and the lack of granulin domain-specific antibodies has hindered the progress of the functional study of PGRN and Grns...
September 29, 2016: Protein Expression and Purification
https://www.readbyqxmd.com/read/27629805/progranulin-overexpression-in-sensory-neurons-attenuates-neuropathic-pain-in-mice-role-of-autophagy
#20
Christine Altmann, Stefanie Hardt, Caroline Fischer, Juliana Heidler, Hee-Young Lim, Annett Häussler, Boris Albuquerque, Béla Zimmer, Christine Möser, Christian Behrends, Frank Koentgen, Ilka Wittig, Mirko H H Schmidt, Albrecht M Clement, Thomas Deller, Irmgard Tegeder
Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis...
September 11, 2016: Neurobiology of Disease
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