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Progranulin

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https://www.readbyqxmd.com/read/29226876/serum-c-peptide-visfatin-resistin-and-ghrelin-are-altered-in-sporadic-and-grn-associated-frontotemporal-lobar-degeneration
#1
Roberta Zanardini, Luisa Benussi, Silvia Fostinelli, Claudia Saraceno, Miriam Ciani, Barbara Borroni, Alessandro Padovani, Giuliano Binetti, Roberta Ghidoni
Frontotemporal lobar degeneration (FTLD) is a group of complex neurodegenerative disease characterized by progressive deterioration of the frontal and anterior temporal lobes of the brain resulting in different heterogeneous conditions, mainly characterized by personality changes, behavioral disturbances, such as binge eating, and deficits in language and executive functions. Null mutations in progranulin gene (GRN) are one of the most frequent genetic determinants in familial frontotemporal dementia. Recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance revealing its metabolic function...
December 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29186428/genome-wide-meta-analysis-identifies-novel-determinants-of-circulating-serum-progranulin
#2
Anke Tönjes, Markus Scholz, Jacqueline Krüger, Kerstin Krause, Dorit Schleinitz, Holger Kirsten, Claudia Gebhardt, Carola Marzi, Harald Grallert, Claes Ladenvall, Henrike Heyne, Esa Laurila, Jennifer Kriebel, Christa Meisinger, Wolfgang Rathmann, Christian Gieger, Leif Groop, Inga Prokopenko, Bo Isomaa, Frank Beutner, Jürgen Kratzsch, Antje Fischer-Rosinsky, Andreas Pfeiffer, Knut Krohn, Joachim Spranger, Joachim Thiery, Matthias Blüher, Michael Stumvoll, Peter Kovacs
Progranulin is a secreted protein with important functions in processes including immune and inflammatory response, metabolism and embryonic development. The present study aimed at identification of genetic factors determining progranulin concentrations.We conducted a genome-wide association meta-analysis for serum progranulin in three independent cohorts from Europe: Sorbs (N = 848) and KORA (N = 1,628) from Germany and PPP-Botnia (N = 335) from Finland (total N = 2,811). SNPs associated with progranulin levels were replicated in two additional German cohorts: LIFE Heart Study (Leipzig; N = 967) and Metabolic Syndrome Berlin Potsdam (Berlin cohort; N = 833)...
November 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29176029/serum-progranulin-levels-in-relation-to-insulin-resistance-in-childhood-obesity
#3
Eman M Alissa, Rima H Sutaih, Hayat Z Kamfar, Abdulmoeen E Alagha, Zuhair M Marzouki
BACKGROUND: Progranulin is an adipokine that is involved in the inflammatory response, glucose metabolism, insulin resistance, and may therefore be involved in chronic subclinical inflammation associated with the pathogenesis of childhood obesity. We aimed to investigate the association of circulating progranulin levels with metabolic parameters in children and to assess the importance of progranulin as a biomarker for metabolic diseases. METHODS: A total of 150 children were consecutively recruited from the Pediatric Nutrition Clinics at King Abdulaziz University Hospital in Jeddah, Saudi Arabia...
November 25, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29150939/mir-34b-5p-inhibition-attenuates-lung-inflammation-and-apoptosis-in-an-lps-induced-acute-lung-injury-mouse-model-by-targeting-progranulin
#4
Wang Xie, Qingchun Lu, Kailing Wang, Jingjing Lu, Xia Gu, Dongyi Zhu, Fanglei Liu, Zhongliang Guo
BACKGROUND: Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS-induced ALI. Here, we have investigated the potential roles of PGRN-targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. METHODS: LPS-induced lung injury and the protective roles of PGRN in ALI were first confirmed...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29149899/selective-depletion-of-microglial-progranulin-in-mice-is-not-sufficient-to-cause-neuronal-ceroid-lipofuscinosis-or-neuroinflammation
#5
Terri L Petkau, Natalia Kosior, Kathleen de Asis, Colúm Connolly, Blair R Leavitt
BACKGROUND: Progranulin deficiency due to heterozygous null mutations in the GRN gene are a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations are thought to be a rare cause of neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout (Grn-null) mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. In the brain, progranulin is predominantly expressed in neurons and microglia, and previously, we demonstrated that neuronal-specific depletion of progranulin does not recapitulate the neuropathological phenotype of Grn-null mice...
November 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29146050/progranulin-plasma-levels-predict-the-presence-of-grn-mutations-in-asymptomatic-subjects-and-do-not-correlate-with-brain-atrophy-results-from-the-genfi-study
#6
Daniela Galimberti, Giorgio G Fumagalli, Chiara Fenoglio, Sara M G Cioffi, Andrea Arighi, Maria Serpente, Barbara Borroni, Alessandro Padovani, Fabrizio Tagliavini, Mario Masellis, Maria Carmela Tartaglia, John van Swieten, Lieke Meeter, Caroline Graff, Alexandre de Mendonça, Martina Bocchetta, Jonathan D Rohrer, Elio Scarpini
We investigated whether progranulin plasma levels are predictors of the presence of progranulin gene (GRN) null mutations or of the development of symptoms in asymptomatic at risk members participating in the Genetic Frontotemporal Dementia Initiative, including 19 patients, 64 asymptomatic carriers, and 77 noncarriers. In addition, we evaluated a possible role of TMEM106B rs1990622 as a genetic modifier and correlated progranulin plasma levels and gray-matter atrophy. Plasma progranulin mean ± SD plasma levels in patients and asymptomatic carriers were significantly decreased compared with noncarriers (30...
November 13, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29124108/an-8-week-open-label-dose-finding-study-of-nimodipine-for-the-treatment-of-progranulin-insufficiency-from-grn-gene-mutations
#7
Sharon J Sha, Zachary A Miller, Sang-Won Min, Yungui Zhou, Jesse Brown, Laura L Mitic, Anna Karydas, Mary Koestler, Richard Tsai, Chiara Corbetta-Rastelli, Sophie Lin, Emma Hare, Scott Fields, Kirsten E Fleischmann, Ryan Powers, Ryan Fitch, Lauren Herl Martens, Mehrdad Shamloo, Anne M Fagan, Robert V Farese, Rodney Pearlman, William Seeley, Bruce L Miller, Li Gan, Adam L Boxer
Introduction: Frontotemporal lobar degeneration-causing mutations in the progranulin (GRN) gene reduce progranulin protein (PGRN) levels, suggesting that restoring PGRN in mutation carriers may be therapeutic. Nimodipine, a Food and Drug Administration-approved blood-brain barrier-penetrant calcium channel blocker, increased PGRN levels in PGRN-deficient murine models. We sought to assess safety and tolerability of oral nimodipine in human GRN mutation carriers. Methods: We performed an open-label, 8-week, dose-finding, phase 1 clinical trial in eight GRN mutation carriers to assess the safety and tolerability of nimodipine and assayed fluid and radiologic markers to investigate therapeutic endpoints...
November 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29116422/progranulin-and-its-biological-effects-in-cancer
#8
REVIEW
Fabian Arechavaleta-Velasco, Carlos Eduardo Perez-Juarez, George L Gerton, Laura Diaz-Cueto
Cancer cells have defects in regulatory mechanisms that usually control cell proliferation and homeostasis. Different cancer cells share crucial alterations in cell physiology, which lead to malignant growth. Tumorigenesis or tumor growth requires a series of events that include constant cell proliferation, promotion of metastasis and invasion, stimulation of angiogenesis, evasion of tumor suppressor factors, and avoidance of cell death pathways. All these events in tumor progression may be regulated by growth factors produced by normal or malignant cells...
November 7, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29098557/loc285629-regulates-cell-proliferation-and-motility-in-colorectal-cancer-cells
#9
S N Nasir, N Abu, N S Ab Mutalib, M Ishak, I Sagap, L Mazlan, I M Rose, R Jamal
PURPOSE: Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated...
November 2, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29096020/elevated-progranulin-contributes-to-synaptic-and-learning-deficit-due-to-loss-of-fragile-x-mental-retardation-protein
#10
Kun Zhang, Yu-Jiao Li, Yanyan Guo, Kai-Yin Zheng, Qi Yang, Le Yang, Xin-Shang Wang, Qian Song, Tao Chen, Min Zhuo, Ming-Gao Zhao
Fragile X syndrome is an inheritable form of intellectual disability caused by loss of fragile X mental retardation protein (FMRP, encoded by the FMR1 gene). Absence of FMRP caused overexpression of progranulin (PGRN, encoded by GRN), a putative tumour necrosis factor receptor ligand. In the present study, we found that progranulin mRNA and protein were upregulated in the medial prefrontal cortex of Fmr1 knock-out mice. In Fmr1 knock-out mice, elevated progranulin caused insufficient dendritic spine pruning and late-phase long-term potentiation in the medial prefrontal cortex of Fmr1 knock-out mice...
October 31, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29067536/development-of-a-cell-based-assay-to-assess-binding-of-the-prongf-prodomain-to-sortilin
#11
Ibrahim Malik, Søren Christensen, Jeffrey B Stavenhagen, Gunnar P H Dietz
Sortilin was first identified based on its activity as part of intracellular protein sorting machinery. Recently, it was discovered that sortilin also acts as a cell surface receptor for the propeptide form of nerve growth factor (proNGF), progranulin, and neurotensin. The interaction of sortilin to these neurotrophic ligands is linked to diseases of the nervous system that lead to neurodegeneration and neuropathic pain. Blocking of the interaction of sortilin to these ligands may prevent or slow the progress of these nervous system disorders...
October 24, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29054751/ng2-cspg4-and-progranulin-in-the-posttraumatic-glial-scar
#12
REVIEW
Michael K E Schäfer, Irmgard Tegeder
Traumatic injury of the central nervous system is one of the leading causes of death and disability in young adults. Failure of regeneration is caused by autonomous neuronal obstacles and by formation of the glial scar, which is essential to seal the injury but also constitutes a barrier for regrowing axons. The scar center is highly inflammatory and populated by NG2+ glia, whereas astrocytes form the sealing border and trap regrowing axons, suggesting that the non-permissive environment of activated astrocytes and extracellular matrix components is one of the reasons for the regenerative failure...
October 17, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29053785/progranulin-a-new-avenue-towards-the-understanding-and-treatment-of-neurodegenerative-disease
#13
Babykumari P Chitramuthu, Hugh P J Bennett, Andrew Bateman
Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene. Progranulin consists of seven and a half, tandemly repeated, non-identical copies of the 12 cysteine granulin motif. Many cellular processes and diseases are associated with this unique pleiotropic factor that include, but are not limited to, embryogenesis, tumorigenesis, inflammation, wound repair, neurodegeneration and lysosome function. Haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to frontotemporal lobar degeneration, a progressive neuronal atrophy that presents in patients as frontotemporal dementia...
August 18, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29044416/disease-and-region-specificity-of-granulin-immunopositivities-in-alzheimer-disease-and-frontotemporal-lobar-degeneration
#14
Qinwen Mao, Dongyang Wang, Yanqing Li, Missia Kohler, Jayson Wilson, Zachary Parton, Bella Shmaltsuyeva, Demirkan Gursel, Rosa Rademakers, Sandra Weintraub, Marek-Marsel Mesulam, Haibin Xia, Eileen H Bigio
Heterozygous loss-of-function mutations in GRN, the progranulin gene, which result in progranulin (PGRN) protein haploinsufficiency, are a major cause of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP). PGRN is composed of seven and a half repeats of a highly conserved granulin motif that is cleaved to produce the granulin peptides A-G and paragranulin. To better understand the role of PGRN and granulin (Grn) peptides in the pathogenesis of neurodegeneration, we evaluated PGRN/Grn in brains of patients with Alzheimer disease, FTLD-TDP type A with or without GRN mutations, and normal individuals, using a panel of monoclonal antibodies against Grn peptides A-G...
November 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29039535/clinical-implications-of-progranulin-in-gastric-cancer-and-its-regulation-via-a-positive-feedback-loop-involving-akt-and-erk-signaling-pathways
#15
Dong Yang, Ruidong Li, Huili Wang, Junye Wang, Lei Han, Lihua Pan, Xueqin Li, Qingli Kong, Guijuan Wang, Xiujun Su
In previous years, progranulin (PGRN) has attracted increasing attention due to its oncogenic roles in several types of tumor. However, the clinical relevance of PGRN in gastric cancer remains to be elucidated. In the present study, 120 retrospective tissue samples were obtained from patients with primary gastric cancer, and the expression of PGRN was detected using immunohistochemistry. The results showed that 71 cases exhibited a high expression of PGRN, which was markedly higher than the 49 cases with a low expression of PGRN...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29036611/progranulin-mediated-deficiency-of-cathepsin-d-results-in-ftd-and-ncl-like-phenotypes-in-neurons-derived-from-ftd-patients
#16
Clarissa Valdez, Yvette C Wong, Michael Schwake, Guojun Bu, Zbigniew K Wszolek, Dimitri Krainc
Frontotemporal dementia (FTD) encompasses a group of neurodegenerative disorders characterized by cognitive and behavioral impairments. Heterozygous mutations in progranulin (PGRN) cause familial FTD and result in decreased PGRN expression, while homozygous mutations result in complete loss of PGRN expression and lead to the neurodegenerative lysosomal storage disorder neuronal ceroid lipofuscinosis (NCL). However, how dose-dependent PGRN mutations contribute to these two different diseases is not well understood...
September 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29031143/c5a-c5ar-pathway-accelerates-renal-ischemia-reperfusion-injury-by-downregulating-pgrn-expression
#17
Kun Zhang, Gui-Qing Li, Qian-Hui He, You Li, Ming Tang, Quan-You Zheng, Gui-Lian Xu, Ke-Qin Zhang
Recent reports indicate that the complement C5a/C5aR pathway and progranulin (PGRN) deficiency both contribute to ischemia-reperfusion (IR)-induced acute kidney injury. However, the underlying relationship between the C5a/C5aR signaling pathway and PGRN expression during acute kidney injury is poorly understood. In this study, we showed that C5aR expression was significantly upregulated after renal IR, and that C5aR deficiency led to a marked increase in PGRN expression and a significant reduction in tubular damage and production of inflammatory cytokines...
October 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28982738/intranasal-administration-of-recombinant-progranulin-inhibits-bronchial-smooth-muscle-hyperresponsiveness-in-mouse-allergic-asthma
#18
Yoshihiko Chiba, Shunta Danno, Rena Suto, Wataru Suto, Yamato Yamane, Motohiko Hanazaki, Hiroshi Katayama, Hiroyasu Sakai
Progranulin (PGRN) is a growth factor with multiple biological functions, and has been suggested as an endogenous inhibitor of TNFα-mediated signaling. TNFα is believed as one of the important mediators of the pathogenesis of asthma, including airway hyperresponsiveness (AHR). In the present study, effects of recombinant PGRN on the TNFα-mediated signaling and the antigen-induced hyper-contractility were examined in bronchial smooth muscles (BSMs) both in vitro and in vivo. Cultured human BSM cells (hBSMCs) and male BALB/c mice were used...
October 5, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28944282/progranulin-acts-as-a-shared-chaperone-and-regulates-multiple-lysosomal-enzymes
#19
Jinlong Jian, Aubryanna Hettinghouse, Chuan-Ju Liu
Multifunctional factor progranulin (PGRN) plays an important role in lysosomes, and its mutations and insufficiency are associated with lysosomal storage diseases, including neuronal ceroid lipofuscinosis and Gaucher disease (GD). The first breakthrough in understanding the molecular mechanisms of PGRN as regulator of lysosomal storage diseases came unexpectedly while investigating the role of PGRN in inflammation. Challenged PGRN null mice displayed typical features of GD. In addition, GRN gene variants were identified in GD patients and the serum levels of PGRN were significantly lower in GD patients...
September 2017: Genes & Diseases
https://www.readbyqxmd.com/read/28916533/sex-differences-in-the-prevalence-of-genetic-mutations-in-ftd-and-als-a-meta-analysis
#20
REVIEW
Ashley F Curtis, Mario Masellis, Ging-Yuek Robin Hsiung, Rahim Moineddin, Kathy Zhang, Bonnie Au, Geneva Millett, Ian Mackenzie, Ekaterina Rogaeva, Mary C Tierney
OBJECTIVE: To conduct a meta-analysis that investigates sex differences in the prevalence of mutations in the 3 most common genes that cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT)-in patients clinically diagnosed with these conditions. METHODS: MEDLINE, EMBASE, and PsycINFO databases were searched (inception to June 30, 2016)...
October 10, 2017: Neurology
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