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Progranulin

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https://www.readbyqxmd.com/read/29665049/protective-effects-of-progranulin-against-focal-cerebral-ischemia-reperfusion-injury-in-rats-by-suppressing-endoplasmic-reticulum-stress-and-nf-%C3%AE%C2%BAb-activation-in-reactive-astrocytes
#1
Qing Shu, Hua Fan, Shi-Jun Li, Dan Zhou, Wei Ma, Xiao-Yan Zhao, Jun-Qiang Yan, Gang Wu
The aim of this study is to explore the effect progranulin (PGRN) has on endoplasmic reticulum (ER) stress and the NF-κB activation in reactive astrocytes found in rat models with focal cerebral ischemia-reperfusion (I/R) injury. Sprague-Dawley (SD) rats were grouped into the sham, I/R, PGRN-high dose, PGRN-low dose, and negative control (NC) groups. TTC staining was applied in order to detect the cerebral infarction volume, a TUNEL assay to detect the apoptosis rate of neurons, an ELISA to measure MDA, SOD, iNOS, LDH, TNF-α, IL-1β, IL-6, and IL-10 levels, and both RT-qPCR and western blotting methods in order to detect PGRN, GFAP, GRP78, CHOP, and NF-κB p65 expressions...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29626829/the-effects-of-adiposity-and-alcohol-use-disorder-on-adipokines-and-biomarkers-of-inflammation-in-depressed-patients
#2
Mari Archer, Onni Niemelä, Mari Hämäläinen, Eeva Moilanen, Esa Leinonen, Olli Kampman
Patients with depression and alcohol use disorder frequently present with elevated markers of inflammation. Adipose tissue may function as a source for inflammation, yet the interplay between adiposity, alcohol use and depression has remained unknown. We examined 242 patients, referred to treatment for depressive symptoms, and followed for a period of 6 months. The assessments included screening for alcohol use and measurements of body mass index, serum adiponectin, leptin, resistin, progranulin, hs-CRP, IL-6 and MCP-1 at baseline and after 6 months of treatment...
March 28, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29625085/progranulin-ameliorates-coxsackievirus-b3-induced-viral-myocarditis-by-downregulating-th1-and-th17-cells
#3
Li Li, Ling Li, Lili Xiao, Jiahong Shangguan
Viral myocarditis, which is caused by Coxsackievirus B3 (CVB3) infection, is a leading reason of sudden cardiac death in young adults. Progranulin (PGRN), a pleiotropic growth factor, has been shown to exert anti-inflammatory function in a variety of inflammatory diseases. However, the expression and function of PGRN in the pathogenesis of viral myocarditis remain largely unknown. In this study, we found that PGRN levels in plasma and cardiac tissues were significantly upregulated post CVB3 infection, and negative correlated with disease severity...
April 3, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29559004/diagnostic-value-of-cerebrospinal-fluid-tau-neurofilament-and-progranulin-in-definite-frontotemporal-lobar-degeneration
#4
Joery Goossens, Maria Bjerke, Sara Van Mossevelde, Tobi Van den Bossche, Johan Goeman, Bart De Vil, Anne Sieben, Jean-Jacques Martin, Patrick Cras, Peter Paul De Deyn, Christine Van Broeckhoven, Julie van der Zee, Sebastiaan Engelborghs
BACKGROUND: We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes. METHODS: CSF levels of routine AD biomarkers (phosphorylated tau (p-tau181 ), total tau (t-tau), and amyloid-beta (Aβ)1-42 ) and neurofilament proteins, as well as progranulin levels in both CSF and serum were quantified in definite FTLD (n = 46), clinical AD (n = 45), and cognitively healthy controls (n = 20)...
March 20, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29555433/rare-nonsynonymous-variants-in-sort1-are-associated-with-increased-risk-for-frontotemporal-dementia
#5
Stéphanie Philtjens, Sara Van Mossevelde, Julie van der Zee, Eline Wauters, Lubina Dillen, Mathieu Vandenbulcke, Rik Vandenberghe, Adrian Ivanoiu, Anne Sieben, Christiana Willems, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Barbara Borroni, Alessandro Padovani, Pau Pastor, Monica Diez-Fairen, Miquel Aguilar, Alexandre de Mendonça, Gabriel Miltenberger-Miltényi, Isabel Hernández, Merce Boada, Agustín Ruiz, Benedetta Nacmias, Sandro Sorbi, Maria Rosário Almeida, Isabel Santana, Jordi Clarimón, Alberto Lleó, Giovanni B Frisoni, Raquel Sanchez-Valle, Albert Lladó, Estrella Gómez-Tortosa, Ellen Gelpi, Marleen Van den Broeck, Karin Peeters, Patrick Cras, Peter P De Deyn, Sebastiaan Engelborghs, Marc Cruts, Christine Van Broeckhoven
We investigated the genetic role of sortilin (SORT1) in frontotemporal dementia (FTD). SORT1 is the neuronal receptor for granulin, encoded by the progranulin gene (GRN), a major causal gene for inherited FTD. In Belgian cohorts of 636 FTD patients and 1066 unaffected control individuals, we identified 5 patient-only nonsynonymous rare variants in SORT1. Rare variant burden analysis showed a significant increase in rare coding variants in patients compared to control individuals (p = 0.04), particularly in the β-propeller domain (p = 0...
February 17, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29545625/gene-therapy-gene-therapy-targets-pathology-in-progranulin-deficient-mice
#6
Ian Fyfe
No abstract text is available yet for this article.
March 16, 2018: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29530724/genetic-and-functional-characters-of-grn-p-t487i-mutation-in-taiwanese-patients-with-atypical-parkinsonian-disorders
#7
Kuo-Hsuan Chang, Guan-Chiun Lee, Chin-Chang Huang, Hung-Chou Kuo, Chiung-Mei Chen, Ya-Chin Hsiao, Hsuan-Chu Hsu, Ke-Jen Hsu, Chih-Hsin Lin, Chia Wen Chang, Guey-Jen Lee-Chen, Yih-Ru Wu
BACKGROUND: Mutations in the GRN (granulin precursor) are a frequent cause of frontotemporal dementia (FTD) and other atypical parkinsonian disorders. However, the frequency of GRN mutations in Asian patients with atypical parkinsonian disorders is still uncertain. METHODS: We screened GRN mutations by sequencing cDNA from 98 patients with FTD or atypical parkinsonian disorders. The functional properties of the identified mutation were evaluated by overexpression in human embryonic kidney (HEK)-293 cells...
February 28, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29524103/the-benefits-of-a-neurogenetics-clinic-in-an-adult-academic-teaching-hospital
#8
Diana A Olszewska, Terri McVeigh, Emer M Fallon, Gregory M Pastores, Tim Lynch
Genetics is the backbone of Neurology, where a number of disorders have a genetic aetiology and are complex, requiring a dedicated Neurogenetics clinic. Genetics in the Republic of Ireland is under-resourced, with the lowest number of consultants per million of population in Europe. In November 2014, we established the monthly adult Neurogenetics clinic in Ireland, staffed by 2 consultants and 2 registrars from each speciality. We see patients with complex rare neurological conditions that may potentially have an underlying genetic basis, in the presence or absence of a family history...
March 9, 2018: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29520145/manic-behavior-and-asymmetric-right-frontotemporal-dementia-from-a-novel-progranulin-mutation
#9
Mario F Mendez
Studies suggest a relationship of manic behavior and bipolar disorder (BD) with behavioral variant frontotemporal dementia (bvFTD). The nature of this relationship is unclear. This report presents a patient with initial manic behavior as the main manifestation of familial bvFTD from a novel progranulin (GRN) mutation. In contrast, there are other reports of a long background of BD preceding a diagnosis of bvFTD. A review of the literature and this patient suggest that manic symptoms result from damage to right frontotemporal neural structures from longstanding BD, as well as from bvFTD and other focal neurological disorders...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29511098/murine-knockin-model-for-progranulin-deficient-frontotemporal-dementia-with-nonsense-mediated-mrna-decay
#10
Andrew D Nguyen, Thi A Nguyen, Jiasheng Zhang, Swathi Devireddy, Ping Zhou, Anna M Karydas, Xialian Xu, Bruce L Miller, Frank Rigo, Shawn M Ferguson, Eric J Huang, Tobias C Walther, Robert V Farese
Frontotemporal dementia (FTD) is the most common neurodegenerative disorder in individuals under age 60 and has no treatment or cure. Because many cases of FTD result from GRN nonsense mutations, an animal model for this type of mutation is highly desirable for understanding pathogenesis and testing therapies. Here, we generated and characterized Grn R493X knockin mice, which model the most common human GRN mutation, a premature stop codon at arginine 493 (R493X). Homozygous Grn R493X mice have markedly reduced Grn mRNA levels, lack detectable progranulin protein, and phenocopy Grn knockout mice, with CNS microgliosis, cytoplasmic TDP-43 accumulation, reduced synaptic density, lipofuscinosis, hyperinflammatory macrophages, excessive grooming behavior, and reduced survival...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29499059/progranulin-serum-levels-in-human-kidney-transplant-recipients-a-longitudinal-study
#11
Bruna Bellincanta Nicoletto, Elis Forcellini Pedrollo, Larissa Salomoni Carpes, Natália Gomes Coloretti, Thaiana Cirino Krolikowski, Gabriela Corrêa Souza, Luiz Felipe Santos Gonçalves, Roberto Ceratti Manfro, Luis Henrique Canani
BACKGROUND: The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. OBJECTIVE: To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. METHODS: Forty-six prospective kidney transplant recipients were included in this longitudinal study...
2018: PloS One
https://www.readbyqxmd.com/read/29480174/decreased-prefrontal-activation-during-matrix-reasoning-in-predementia-progranulin-mutation-carriers
#12
Courtney Alexander, Dagmar Zeithamova, Ging-Yuek R Hsiung, Ian R Mackenzie, Claudia Jacova
We tested the potential of task-based functional neuroimaging as a biomarker of emerging prefrontal brain changes in progranulin (GRN) mutations carriers. Five GRN mutation carriers free of frontotemporal dementia (FTD) and 11 non-carriers from families with FTD-GRN underwent functional MRI while solving matrix-reasoning problems. Mutation carriers displayed slower responses for more difficult problems and lower lateral prefrontal activation across all problems. Overall task-evoked posterior ventrolateral prefrontal activation predicted mutation status with 100% sensitivity and 91% specificity...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29475178/progranulin-facilitates-the-increase-of-platelet-count-in-immune-thrombocytopenia
#13
Yingyi Yu, Yuanyuan Shi, Xinyi Zuo, Qi Feng, Yu Hou, Wei Tang, Yi Lu, Fan Yi, Ming Hou, Yuan Yu, Jun Peng
INTRODUCTION: Progranulin (PGRN) is emerging as a critical immune mediator involved in a variety of autoimmune disorders. However, its role in immune thrombocytopenia (ITP) remains unclear. MATERIALS AND METHODS: In this study, the enzyme-linked immunosorbent assay was used for determining the plasma levels of PGRN in ITP patients vs. healthy controls. In addition, the role of PGRN in ITP was investigated in two kinds of ITP murine models. Further, we explored whether PGRN functioned by affecting the number of T regulatory cells (Tregs) using flow cytometry...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29452214/pgrn-promotes-lymphangiogenesis-through-vegf-c-and-is-an-independent-risk-factor-in-human-esophageal-cancers
#14
Guanhua Li, Taotao Dong, Dong Yang, Aiqin Gao, Judong Luo, Hongyan Yang, Linlin Wang
Lymph node metastasis is one of the most important predictor of the prognosis for esophageal cancer (EC) patients. Yet, the mechanism underlying the lymph node metastasis is largely unknown. Progranulin (PGRN) is shown to be highly expressed in various types of cancers and could promote the angiogenesis and epithelial mesenchymal transition (EMT) of cancer cells in previous studies. However, the expression status of PGRN and its effects on the lymphangiogenesis in EC is largely unclear. In this study, we show for the first time that PGRN is expressed in EC tissue samples and cell lines and could promote the expression of VEGF-C in vitro, a well-known lymphangiogenesis inducer, through the putative signaling transducers p-ERK and p-AKT...
February 13, 2018: Human Pathology
https://www.readbyqxmd.com/read/29434051/downregulation-of-exosomal-mir-204-5p-and-mir-632-as-a-biomarker-for-ftd-a-genfi-study
#15
Raphael Schneider, Paul McKeever, TaeHyung Kim, Caroline Graff, John Cornelis van Swieten, Anna Karydas, Adam Boxer, Howie Rosen, Bruce L Miller, Robert Laforce, Daniela Galimberti, Mario Masellis, Barbara Borroni, Zhaolei Zhang, Lorne Zinman, Jonathan Daniel Rohrer, Maria Carmela Tartaglia, Janice Robertson
OBJECTIVE: To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD. METHODS: GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier...
February 6, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29408220/a-potent-tilapia-secreted-granulin-peptide-enhances-the-survival-of-transgenic-zebrafish-infected-by-vibrio-vulnificus-via-modulation-of-innate-immunity
#16
Sheng-Han Wu, Hong-Jie Lin, Wen-Fu Lin, Jen-Leih Wu, Hong-Yi Gong
Progranulin (PGRN) is a multi-functional growth factor that mediates cell proliferation, survival, migration, tumorigenesis, wound healing, development, and anti-inflammation activity. A novel alternatively spliced transcript from the short-form PGRN1 gene encoding a novel, secreted GRN peptide composed of 20-a.a. signal peptide and 41-a.a. GRN named GRN-41 was identified to be abundantly expressed in immune-related organs including spleen, head kidney, and intestine of Mozambique tilapia. The expression of GRN-41 and PGRN1 were further induced in the spleen of tilapia challenged with Vibrio vulnificus at 3 h post infection (hpi) and 6 hpi, respectively...
February 2, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29403285/progranulin-modulates-cholangiocarcinoma-cell-proliferation-apoptosis-and-motility-via-the-pi3k-pakt-pathway
#17
Minerva Daya, Watcharin Loilome, Anchalee Techasen, Malinee Thanee, Prakasit Sa-Ngiamwibool, Attapol Titapun, Puangrat Yongvanit, Nisana Namwat
Progranulin (PGRN) is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA). However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29398357/retrograde-signaling-from-progranulin-to-sort1-counteracts-synapse-elimination-in-the-developing-cerebellum
#18
Naofumi Uesaka, Manabu Abe, Kohtarou Konno, Maya Yamazaki, Kazuto Sakoori, Takaki Watanabe, Tzu-Huei Kao, Takayasu Mikuni, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano
Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16...
January 26, 2018: Neuron
https://www.readbyqxmd.com/read/29396296/chitinase-3-like-protein-1-a-progranulin-downstream-molecule-and-potential-biomarker-for-gaucher-disease
#19
Jinlong Jian, Yuehong Chen, Rossella Liberti, Wenyu Fu, Wenhuo Hu, Rachel Saunders-Pullman, Gregory M Pastores, Ying Chen, Ying Sun, Gregory A Grabowski, Chuan-Ju Liu
We recently reported that progranulin (PGRN) is a novel regulator of glucocerebrosidase and its deficiency associates with Gaucher Diseases (GD) (Jian et al., 2016a; Jian et al., 2018). To isolate the relevant downstream molecules, we performed a whole genome microarray and mass spectrometry analysis, which led to the isolation of Chitinase-3-like-1 (CHI3L1) as one of the up-regulated genes in PGRN null mice. Elevated levels of CHI3L1 were confirmed by immunoblotting and immunohistochemistry. In contrast, treatment with recombinant Pcgin, a derivative of PGRN, as well as imigluerase, significantly reduced the expressions of CHI3L1 in both PGRN null GD model and the fibroblasts from GD patients...
January 30, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29382817/targeting-tyro3-ameliorates-a-model-of-pgrn-mutant-ftld-tdp-via-tau-mediated-synaptic-pathology
#20
Kyota Fujita, Xigui Chen, Hidenori Homma, Kazuhiko Tagawa, Mutsuki Amano, Ayumu Saito, Seiya Imoto, Hiroyasu Akatsu, Yoshio Hashizume, Kozo Kaibuchi, Satoru Miyano, Hitoshi Okazawa
Mutations in the progranulin (PGRN) gene cause a tau pathology-negative and TDP43 pathology-positive form of frontotemporal lobar degeneration (FTLD-TDP). We generated a knock-in mouse harboring the R504X mutation (PGRN-KI). Phosphoproteomic analysis of this model revealed activation of signaling pathways connecting PKC and MAPK to tau prior to TDP43 aggregation and cognitive impairments, and identified PKCα as the kinase responsible for the early-stage tau phosphorylation at Ser203. Disinhibition of Gas6 binding to Tyro3 due to PGRN reduction results in activation of PKCα via PLCγ, inducing tau phosphorylation at Ser203, mislocalization of tau to dendritic spines, and spine loss...
January 30, 2018: Nature Communications
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