keyword
MENU ▼
Read by QxMD icon Read
search

Neuroserpin

keyword
https://www.readbyqxmd.com/read/27639894/physiological-and-pathological-functions-of-neuroserpin-regulation-of-cellular-responses-through-multiple-mechanisms
#1
Tet Woo Lee, Vicky W K Tsang, Evert Jan Loef, Nigel P Birch
It is 27 years since neuroserpin was first discovered in the nervous system and identified as a member of the serpin superfamily. Since that time potential roles for this serine protease inhibitor have been identified in neuronal and non-neuronal systems. Many are linked to inhibition of neuroserpin's principal enzyme target, tissue plasminogen activator (tPA), although some have been suggested to involve alternate non-inhibitory mechanisms. This review focuses mainly on the inhibitory roles of neuroserpin and discusses the evidence supporting tPA as the physiological target...
September 14, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27618835/progressive-myoclonus-epilepsy-associated-with-neuroserpin-inclusion-bodies-neuroserpinosis
#2
Benoit D Roussel, David A Lomas, Damian C Crowther
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a conformational proteinopathy characterised by neuronal inclusion bodies composed of the serine protease inhibitor (SERPIN), neuroserpin. Presenting clinically as a familial dementia-epilepsy syndrome, the molecular mechanism of the pathogenic abnormalities in neuroserpin has been characterised at atomic resolution. There is a remarkable genotype-phenotype correlation between the degree of molecular destabilisation of the several variants of the neuroserpin protein, their propensity to self-associate and the age of onset of the dementia-epilepsy complex...
September 1, 2016: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/27510267/neuroserpin-attenuates-h2o2-induced-oxidative-stress-in-hippocampal-neurons-via-akt-and-bcl-2-signaling-pathways
#3
Yong Cheng, Y Peng Loh, Nigel P Birch
Oxidative stress plays a critical role in neuronal injury and is associated with various neurological diseases. Here, we explored the potential protective effect of neuroserpin against oxidative stress in primary cultured hippocampal neurons. Our results show that neuroserpin inhibits H2O2-induced neurotoxicity in hippocampal cultures as measured by WST, LDH release, and TUNEL assays. We found that neuroserpin enhanced the activation of AKT in cultures subjected to oxidative stress and that the AKT inhibitor Ly294002 blocked this neuroprotective effect...
August 11, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27452424/an-inflammatory-and-trophic-disconnect-biomarker-profile-revealed-in-down-syndrome-plasma-relation-to-cognitive-decline-and-longitudinal-evaluation
#4
M Florencia Iulita, Alison Ower, Concetta Barone, Rowan Pentz, Palma Gubert, Corrado Romano, Rita Anna Cantarella, Flaviana Elia, Serafino Buono, Marilena Recupero, Carmelo Romano, Sabrina Castellano, Paolo Bosco, Santo Di Nuovo, Filippo Drago, Filippo Caraci, A Claudio Cuello
INTRODUCTION: Given that Alzheimer's pathology develops silently over decades in Down syndrome (DS), prognostic biomarkers of dementia are a major need. METHODS: We investigated the plasma levels of Aβ, proNGF, tPA, neuroserpin, metallo-proteases and inflammatory molecules in 31 individuals with DS (with and without dementia) and in 31 healthy controls. We examined associations between biomarkers and cognitive decline. RESULTS: Aβ40 and Aβ42 were elevated in DS plasma compared to controls, even in DS individuals without dementia...
July 21, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27378851/neuroserpin-differentiates-between-forms-of-tissue-type-plasminogen-activator-via-ph-dependent-deacylation
#5
Karen-Sue B Carlson, Lan Nguyen, Kat Schwartz, Daniel A Lawrence, Bradford S Schwartz
Tissue-type plasminogen activator (t-PA), initially characterized for its critical role in fibrinolysis, also has key functions in both physiologic and pathologic processes in the CNS. Neuroserpin (NSP) is a t-PA specific serine protease inhibitor (serpin) found almost exclusively in the CNS that regulates t-PA's proteolytic activity and protects against t-PA mediated seizure propagation and blood-brain barrier disruption. This report demonstrates that NSP inhibition of t-PA varies profoundly as a function of pH within the biologically relevant pH range for the CNS, and reflects the stability, rather than the formation of NSP: t-PA acyl-enzyme complexes...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27301418/plasmin-and-regulators-of-plasmin-activity-control-the-migratory-capacity-and-adhesion-of-human-t-cells-and-dendritic-cells-by-regulating-cleavage-of-the-chemokine-ccl21
#6
Natalie Lorenz, Evert Jan Loef, Inken D Kelch, Daniel J Verdon, Moyra M Black, Martin J Middleditch, David R Greenwood, E Scott Graham, Anna Es Brooks, P Rod Dunbar, Nigel P Birch
The homeostatic chemokine CCL21 has a pivotal role in lymphocyte homing and compartment localisation within the lymph node, and also affects adhesion between immune cells. The effects of CCL21 are modulated by its mode of presentation, with different cellular responses seen for surface-bound and soluble forms. Here we show that plasmin cleaves surface-bound CCL21 to release the C-terminal peptide responsible for CCL21 binding to glycosaminoglycans on the extracellular matrix and cell surfaces, thereby generating the soluble form...
August 2, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27035834/neuroserpin-protects-rat-neurons-and-microglia-mediated-inflammatory-response-against-oxygen-glucose-deprivation-and-reoxygenation-treatments-in-an-in-vitro-study
#7
Xuelian Yang, Tetsuya Asakawa, Sha Han, Ling Liu, Wei Li, Weiwen Wu, Yunhe Luo, Wenjie Cao, Xin Cheng, Baoguo Xiao, Hiroki Namba, Chuanzhen Lu, Qiang Dong, Liang Wang
BACKGROUND/AIMS: Neuroserpin (NSP) is known for its neuroprotective role in cerebral ischemic animal models and patients. Our laboratory conducted a series of investigations on the neuroprotection of NSP in different cells in the brain. In the present study, we further observe the effects of NSP on neurons and microglia-mediated inflammatory response following oxygen-glucose deprivation (OGD), and explore possible mechanisms related to neuroprotection of OGD in the central nervous system (CNS)...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/26733586/limited-unfolded-protein-response-and-inflammation-in-neuroserpinopathy
#8
Irene López-González, Alberto Pérez-Mediavilla, Marta Zamarbide, Margarita Carmona, Benjamin Torrejón Escribano, Markus Glatzel, Giovanna Galliciotti, Isidre Ferrer
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare disease characterized by the deposition of multiple intracytoplasmic neuronal inclusions that contain mutated neuroserpin. Tg-Syracuse (Tg-Syr) mice express Ser49Pro mutated neuroserpin and develop clinical and neuropathological features of human FENIB. We used 8-, 34-, 45- and 80-week-old Tg-Syr mice to characterize neuroinflammation and the unfolded protein response (UPR) in a neurodegenerative disease in which abnormal protein aggregates accumulate within the endoplasmic reticulum (ER)...
February 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/26732982/embelin-binds-to-human-neuroserpin-and-impairs-its-polymerisation
#9
Giorgia Saga, Fabio Sessa, Alberto Barbiroli, Carlo Santambrogio, Rosaria Russo, Michela Sala, Samuele Raccosta, Vincenzo Martorana, Sonia Caccia, Rosina Noto, Claudia Moriconi, Elena Miranda, Rita Grandori, Mauro Manno, Martino Bolognesi, Stefano Ricagno
Neuroserpin (NS) is a serpin inhibitor of tissue plasminogen activator (tPA) in the brain. The polymerisation of NS pathologic mutants is responsible for a genetic dementia known as familial encephalopathy with neuroserpin inclusion bodies (FENIB). So far, a pharmacological treatment of FENIB, i.e. an inhibitor of NS polymerisation, remains an unmet challenge. Here, we present a biophysical characterisation of the effects caused by embelin (EMB a small natural compound) on NS conformers and NS polymerisation...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26620556/reactive-center-loop-rcl-peptides-derived-from-serpins-display-independent-coagulation-and-immune-modulating-activities
#10
Sriram Ambadapadi, Ganesh Munuswamy-Ramanujam, Donghang Zheng, Colin Sullivan, Erbin Dai, Sufi Morshed, Baron McFadden, Emily Feldman, Melissa Pinard, Robert McKenna, Scott Tibbetts, Alexandra Lucas
Serpins regulate coagulation and inflammation, binding serine proteases in suicide-inhibitory complexes. Target proteases cleave the serpin reactive center loop scissile P1-P1' bond, resulting in serpin-protease suicide-inhibitory complexes. This inhibition requires a near full-length serpin sequence. Myxomavirus Serp-1 inhibits thrombolytic and thrombotic proteases, whereas mammalian neuroserpin (NSP) inhibits only thrombolytic proteases. Both serpins markedly reduce arterial inflammation and plaque in rodent models after single dose infusion...
February 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26559654/not-all-inner-ears-are-the-same-otolith-matrix-proteins-in-the-inner-ear-of-sub-adult-cichlid-fish-oreochromis-mossambicus-reveal-insights-into-the-biomineralization-process
#11
Jochen Weigele, Tamara A Franz-Odendaal, Reinhard Hilbig
The fish ear stones (otoliths) consist mainly of calcium carbonate and have lower amounts of a proteinous matrix. This matrix consists of macromolecules, which directly control the biomineralization process. We analyzed the composition of this proteinous matrix by mass spectrometry in a shotgun approach. For this purpose, an enhanced protein purification technique was developed that excludes any potential contamination of proteins from body fluids. Using this method we identified eight proteins in the inner ear of Oreochromis mossambicus...
February 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/26528129/physiological-and-pathological-roles-of-tissue-plasminogen-activator-and-its-inhibitor-neuroserpin-in-the-nervous-system
#12
REVIEW
Tet Woo Lee, Vicky W K Tsang, Nigel P Birch
Although its roles in the vascular space are most well-known, tissue plasminogen activator (tPA) is widely expressed in the developing and adult nervous system, where its activity is believed to be regulated by neuroserpin, a predominantly brain-specific member of the serpin family of protease inhibitors. In the normal physiological state, tPA has been shown to play roles in the development and plasticity of the nervous system. Ischemic damage, however, may lead to excess tPA activity in the brain and this is believed to contribute to neurodegeneration...
2015: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/26367528/interactions-between-n-linked-glycosylation-and-polymerisation-of-neuroserpin-within-the-endoplasmic-reticulum
#13
Claudia Moriconi, Adriana Ordoñez, Giuseppe Lupo, Bibek Gooptu, James A Irving, Rosina Noto, Vincenzo Martorana, Mauro Manno, Valentina Timpano, Noemi A Guadagno, Lucy Dalton, Stefan J Marciniak, David A Lomas, Elena Miranda
The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease...
December 2015: FEBS Journal
https://www.readbyqxmd.com/read/26329378/the-stability-and-activity-of-human-neuroserpin-are-modulated-by-a-salt-bridge-that-stabilises-the-reactive-centre-loop
#14
Rosina Noto, Loredana Randazzo, Samuele Raccosta, Sonia Caccia, Claudia Moriconi, Elena Miranda, Vincenzo Martorana, Mauro Manno
Neuroserpin (NS) is an inhibitory protein belonging to the serpin family and involved in several pathologies, including the dementia Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB), a genetic neurodegenerative disease caused by accumulation of NS polymers. Our Molecular Dynamics simulations revealed the formation of a persistent salt bridge between Glu289 on strand s2C and Arg362 on the Reactive Centre Loop (RCL), a region important for the inhibitory activity of NS. Here, we validated this structural feature by simulating the Glu289Ala mutant, where the salt bridge is not present...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26273685/identification-of-a-neurovascular-signaling-pathway-regulating-seizures-in-mice
#15
Linda Fredriksson, Tamara K Stevenson, Enming J Su, Margaret Ragsdale, Shannon Moore, Stefan Craciun, Gerald P Schielke, Geoffrey G Murphy, Daniel A Lawrence
OBJECTIVE: A growing body of evidence suggests that increased blood-brain barrier (BBB) permeability can contribute to the development of seizures. The protease tissue plasminogen activator (tPA) has been shown to promote BBB permeability and susceptibility to seizures. In this study, we examined the pathway regulated by tPA in seizures. METHODS: An experimental model of kainate-induced seizures was used in genetically modified mice, including mice deficient in tPA (tPA (-/-) ), its inhibitor neuroserpin (Nsp (-/-) ), or both (Nsp:tPA (-/-) ), and in mice conditionally deficient in the platelet-derived growth factor receptor alpha (PDGFRα)...
July 2015: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/26176694/retina-is-protected-by-neuroserpin-from-ischemic-reperfusion-induced-injury-independent-of-tissue-type-plasminogen-activator
#16
R P Gu, L L Fu, C H Jiang, Y F Xu, X Wang, J Yu
The purpose of the present study was to investigate the potential neuroprotective effect of neuroserpin (NSP) on acute retinal ischemic/reperfusion-induced (IR) injury. An IR injury model was established by elevating intraocular pressure (IOP) for 60 minutes in wild type and tPA-deficient (tPA-/-) mice. Prior to IR injury, 1 μL of 20 μmol/L NSP or an equal volume of bovine serum albumin (BSA) was intravitreally administered. Retinal function was evaluated by electroretinograph (ERG) and the number of apoptotic neurons was determined via TUNEL labeling...
2015: PloS One
https://www.readbyqxmd.com/read/26152395/quantitative-proteomics-suggests-decrease-in-the-secretogranin-1-cerebrospinal-fluid-levels-during-the-disease-course-of-multiple-sclerosis
#17
Ann C Kroksveen, Jacob D Jaffe, Elise Aasebø, Harald Barsnes, Yngvild Bjørlykke, Diego Franciotta, Hasmik Keshishian, Kjell-Morten Myhr, Jill A Opsahl, Vincent van Pesch, Charlotte E Teunissen, Øivind Torkildsen, Rune J Ulvik, Heidrun Vethe, Steven A Carr, Frode S Berven
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS with unknown cause. Proteins with different abundance in the cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients and neurological controls could give novel insight to the MS pathogenesis and be used to improve diagnosis, predict prognosis and disease course, and guide in therapy decisions. We combined iTRAQ labeling and Orbitrap mass spectrometry to discover proteins with different CSF abundance between six RRMS patients and 18 neurological disease controls...
October 2015: Proteomics
https://www.readbyqxmd.com/read/25961991/molecular-bases-of-neuroserpin-function-and-pathology
#18
Sonia Caccia, Stefano Ricagno, Martino Bolognesi
Serpins build a large and evolutionary widespread protein superfamily, hosting members that are mainly Ser-protease inhibitors. Typically, serpins display a conserved core domain composed of three main β-sheets and 9-10 α-helices, for a total of approximately 350 amino acids. Neuroserpin (NS) is mostly expressed in neurons and in the central and peripheral nervous systems, where it targets tissue-type plasminogen activator. NS activity is relevant for axogenesis, synaptogenesis and synaptic plasticity. Five (single amino acid) NS mutations are associated with severe neurodegenerative disease in man, leading to early onset dementia, epilepsy and neuronal death...
August 1, 2010: Biomolecular Concepts
https://www.readbyqxmd.com/read/25874935/neuroprotective-effect-of-neuroserpin-in-oxygen-glucose-deprivation-and-reoxygenation-treated-rat-astrocytes-in-vitro
#19
Liang Wang, Yang Zhang, Tetsuya Asakawa, Wei Li, Sha Han, Qinying Li, Baoguo Xiao, Hiroki Namba, Chuanzhen Lu, Qiang Dong
Neuroserpin (NSP) reportedly exerts neuroprotective effects in cerebral ischemic animal models and patients; however, the mechanism of protection is poorly understood. We thus attempted to confirm neuroprotective effects of NSP on astrocytes in the ischemic state and then explored the relative mechanisms. Astrocytes from neonatal rats were treated with oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R). To confirm the neuroprotective effects of NSP, we measured the cell survival rate, relative lactate dehydrogenase (LDH) release; we also performed morphological methods, namely Hoechst 33342 staining and Annexin V assay...
2015: PloS One
https://www.readbyqxmd.com/read/25859180/secretory-function-in-subplate-neurons-during-cortical-development
#20
Shinichi Kondo, Hannah Al-Hasani, Anna Hoerder-Suabedissen, Wei Zhi Wang, Zoltán Molnár
Subplate cells are among the first generated neurons in the mammalian cerebral cortex and have been implicated in the establishment of cortical wiring. In rodents some subplate neurons persist into adulthood. Here we would like to highlight several converging findings which suggest a novel secretory function of subplate neurons during cortical development. Throughout the postnatal period in rodents, subplate neurons have highly developed rough endoplasmic reticulum (ER) and are under an ER stress condition...
2015: Frontiers in Neuroscience
keyword
keyword
96840
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"