Saftig, Paul

[["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Arthritis & Rheumatism"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Schurigt, U."],["dc.contributor.author","Hummel, Klaus M."],["dc.contributor.author","Middel, PKPP"],["dc.contributor.author","Schroder, H. E."],["dc.contributor.author","Saftig, P."],["dc.contributor.author","Kollias, G."],["dc.contributor.author","Brauer, R."],["dc.date.accessioned","2018-11-07T10:45:46Z"],["dc.date.available","2018-11-07T10:45:46Z"],["dc.date.issued","2004"],["dc.format.extent","S284"],["dc.identifier.isi","000223799000719"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47582"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.publisher.place","Hoboken"],["dc.relation.conference","68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals"],["dc.relation.eventlocation","San Antonio, TX"],["dc.relation.issn","0004-3591"],["dc.title","Cathepsin K deficiency does not prevent bone destruction in TNF transgenic mice"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Bone and Mineral Research"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Everts, V."],["dc.contributor.author","Suter, A."],["dc.contributor.author","von Figura, Kurt"],["dc.contributor.author","Beertsen, W."],["dc.contributor.author","Saftig, P."],["dc.date.accessioned","2018-11-07T08:42:46Z"],["dc.date.available","2018-11-07T08:42:46Z"],["dc.date.issued","2001"],["dc.format.extent","S451"],["dc.identifier.isi","000170709001316"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19779"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Bone & Mineral Res"],["dc.publisher.place","Washington"],["dc.relation.issn","0884-0431"],["dc.title","Acid phosphatase deficiency leads to accumulation of osteopontin in the subosteoclastic resorption area."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Cleutjens, K. B."],["dc.contributor.author","Lutgens, E."],["dc.contributor.author","Sijbers, A. M."],["dc.contributor.author","Faber, B. C."],["dc.contributor.author","Black, D."],["dc.contributor.author","Organon, N. V."],["dc.contributor.author","Long, C. J."],["dc.contributor.author","Fisher, A."],["dc.contributor.author","Saftig, P."],["dc.contributor.author","Daemen, M. J."],["dc.date.accessioned","2018-11-07T09:49:40Z"],["dc.date.available","2018-11-07T09:49:40Z"],["dc.date.issued","2002"],["dc.format.extent","121"],["dc.identifier.isi","000179142700645"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35552"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","American-Heart-Association Abstracts From Scientific Sessions"],["dc.relation.eventlocation","CHICAGO, ILLINOIS"],["dc.relation.issn","0009-7322"],["dc.title","Targeted disruption of the cathepsin K gene results in reduced atherosclerotic plaque progression"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Vincent, B."],["dc.contributor.author","Paitel, E."],["dc.contributor.author","Lopez-Perez, E."],["dc.contributor.author","Checler, F."],["dc.contributor.author","Saftig, P."],["dc.contributor.author","Frobert, Y."],["dc.contributor.author","Grassi, J."],["dc.contributor.author","Hartmann, Daniel"],["dc.contributor.author","De Strooper, B."],["dc.date.accessioned","2018-11-07T10:23:17Z"],["dc.date.available","2018-11-07T10:23:17Z"],["dc.date.issued","2002"],["dc.format.extent","S70"],["dc.identifier.isi","000177465300261"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42427"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.issn","0197-4580"],["dc.title","Physiological processing of the prion protein: Regulation by protein kinase c agonists and involvement of disintegrins"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","422"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","432"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Caeyenberghs, Karen"],["dc.contributor.author","Balschun, Detlef"],["dc.contributor.author","Roces, Diego Prieto"],["dc.contributor.author","Schwake, Michael"],["dc.contributor.author","Saftig, Paul"],["dc.contributor.author","D'Hooge, Rudi"],["dc.date.accessioned","2018-11-07T09:30:19Z"],["dc.date.available","2018-11-07T09:30:19Z"],["dc.date.issued","2006"],["dc.description.abstract","alpha-Mannosidosis is a lysosomal storage disorder caused by lysosomal alpha-mannosidase (LAMAN) deficiency that leads to neurocognitive dysfunctions, psychotic symptoms and emotional changes in human patients. A murine mannosidosis model, LAMAN-deficient mice, was examined on a behavioral task battery that included test for neuromotor, exploratory and neurocognitive (spatial learning and memory) abilities, and multivariate statistical analyses were used to identify behavioral and neurocognitive domains that are most heavily affected by LAMAN deficiency. In addition, we further investigated synaptic plasticity recordings on hippocampal slices that may relate to these behavioral alterations. Correlation analysis revealed significant intra- and intertask correlations and factor analysis that included all 21 behavioral variables identified three main factors (exploration/emotionality, locomotion and learning/memory abilities). Significant correlations were observed between genotype, and factor 1 (exploration/emotionality) and factor 3 (learning/memory abilities). Discriminant function analysis showed that \"path length in the open field test\" and \"time spent in the target quadrant during the water maze probe trial\" were the most decisive variables to distinguish between the genotypes. We therefore suggest that these variables would be especially important in forthcoming therapy assessment experiments using this murine mannosidosis model. LAMAN-deficient mice displayed severe changes in synaptic plasticity, which may have contributed to the neurocognitive impairments observed. The present report further shows that targeted deletion of the LAMAN gene in mice mimics many aspects of human alpha-mannosidosis, and these data provide a basis for future therapeutic experiments. (c) 2006 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2006.03.009"],["dc.identifier.isi","000239611700017"],["dc.identifier.pmid","16766199"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31280"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","0969-9961"],["dc.title","Multivariate neurocognitive and emotional profile of a mannosidosis murine model for therapy assessment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1398"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","1411"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Schneppenheim, Janna"],["dc.contributor.author","Huettl, Susann"],["dc.contributor.author","Mentrup, Torben"],["dc.contributor.author","Luellmann-Rauch, Renate"],["dc.contributor.author","Rothaug, Michelle"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Araki, Masatake"],["dc.contributor.author","Araki, Kimi"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Fluhrer, Regina"],["dc.contributor.author","Saftig, Paul"],["dc.contributor.author","Schroeder, Bernd"],["dc.date.accessioned","2018-11-07T09:42:09Z"],["dc.date.available","2018-11-07T09:42:09Z"],["dc.date.issued","2014"],["dc.description.abstract","We reported recently that the presenilin homologue signal peptide peptidase-like 2a (SPPL2a) is essential for B cell development by cleaving the N-terminal fragment (NTF) of the invariant chain (li, CD74). Based on this, we suggested that pharmacological modulation of SPPL2a may represent a novel approach to deplete B cells in autoimmune disorders. With regard to reported overlapping substrate spectra of SPPL2a and its close homologue, SPPL2b, we investigated the role of SPPL2b in CD74 NTF proteolysis and its impact on B and dendritic cell homeostasis. In heterologous expression experiments, SPPL2b was found to cleave CD74 NTF with an efficiency simliar to that of SPPL2a. For in vivo analysis, SPPL2b single-deficient and SPPL2a/SPPL2b double-deficient mice were generated and examined for CD74 NTF turnover/accumulation, B cell maturation and functionality, and dendritic cell homeostasis. We demonstrate that in vivo SPPL2b does not exhibit a physiologically relevant contribution to CD74 proteolysis in B and dendritic cells. Furthermore, we reveal that both proteases exhibit divergent subcellular localizations in B cells and different expression profiles in murine tissues. These findings suggest distinct functions of SPPL2a and SPPL2b and, based on a high abundance of SPPL2b in brain, a physiological role of this protease in the central nervous system."],["dc.identifier.doi","10.1128/MCB.00038-14"],["dc.identifier.isi","000333338600003"],["dc.identifier.pmid","24492962"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33889"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","1098-5549"],["dc.relation.issn","0270-7306"],["dc.title","The Intramembrane Proteases Signal Peptide Peptidase-Like 2a and 2b Have Distinct Functions In Vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Hartmann, Daniel"],["dc.contributor.author","De Strooper, B."],["dc.contributor.author","Serneels, L."],["dc.contributor.author","Craessaerts, K."],["dc.contributor.author","Herreman, A."],["dc.contributor.author","Annaert, W."],["dc.contributor.author","Brabant, V."],["dc.contributor.author","Luebke, Torben"],["dc.contributor.author","Illert, A. L."],["dc.contributor.author","von Figura, Kurt"],["dc.contributor.author","Saftig, P."],["dc.date.accessioned","2018-11-07T10:23:07Z"],["dc.date.available","2018-11-07T10:23:07Z"],["dc.date.issued","2002"],["dc.format.extent","S183"],["dc.identifier.isi","000177465300670"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42396"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.issn","0197-4580"],["dc.title","Deficiency for the disintegrin metalloprotease ADAM10 causes disturbed alpha-secretase function and a notch deficiency-related phenotype in mice"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","897"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cell Biology International"],["dc.bibliographiccitation.lastpage","902"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Schellens, JPM"],["dc.contributor.author","Saftig, P."],["dc.contributor.author","von Figura, Kurt"],["dc.contributor.author","Everts, V."],["dc.date.accessioned","2018-11-07T10:42:09Z"],["dc.date.available","2018-11-07T10:42:09Z"],["dc.date.issued","2003"],["dc.description.abstract","Transport of lysosomal enzymes is mediated by two mannose 6-phosphate receptors: a cation dependent (CD-MPR) and a cation independent receptor (CI-MPR). In the present study the effect of MPR-deficiency on the lysosomal system of neonatal mouse hepatocytes was studied by ultrastructural morphometric analyses. The volume density of the lysosomal system in hepatocytes of mice that lack both receptors was significantly increased in comparison with controls and with mice deficient for CI-MPR only. This higher volume density was due to a nine-fold increase of residual bodies. In CI-MPR-deficient mice the volume density of the lysosomal system was not different from controls and no increase of residual bodies was observed. It is concluded that in hepatocytes of MPR-deficient neonatal mice lysosomal storage occurs when both MPRs are lacking, whereas deficiency of CI-MPR only has no effect on the ultrastructure of the lysosomal system. (C) 2003 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.cellbi.2003.07.001"],["dc.identifier.isi","000186532600002"],["dc.identifier.pmid","14585283"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46721"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Ltd Elsevier Science Ltd"],["dc.relation.issn","1065-6995"],["dc.title","Deficiency of mannose 6-phosphate receptors and lysosomal storage: a morphometric analysis of hepatocytes of neonatal mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3355"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Molecular Biology of the Cell"],["dc.bibliographiccitation.lastpage","3368"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Eskelinen, E. L."],["dc.contributor.author","Illert, A. L."],["dc.contributor.author","Tanaka, Y."],["dc.contributor.author","Schwarzmann, G."],["dc.contributor.author","Blanz, J."],["dc.contributor.author","von Figura, Kurt"],["dc.contributor.author","Saftig, P."],["dc.date.accessioned","2018-11-07T10:07:50Z"],["dc.date.available","2018-11-07T10:07:50Z"],["dc.date.issued","2002"],["dc.description.abstract","In LAMP-2-deficient mice autophagic vacuoles accumulate in many tissues, including liver, pancreas, muscle, and heart. Here we extend the phenotype analysis using cultured hepatocytes. In LAMP-2-deficient hepatocytes the half-life of both early and late autophagic vacuoles was prolonged as evaluated by quantitative electron microscopy. However, an endocytic tracer reached the autophagic vacuoles, indicating delivery of endo/lysosomal constituents to autophagic vacuoles. Enzyme activity measurements showed that the trafficking of some lysosomal enzymes to lysosomes was impaired.,Immunoprecipitation of metabolically labeled cathepsin D indicated reduced intracellular retention and processing in the knockout cells. The steady-state level of 300-kDa mannose 6-phosphate receptor was slightly lower in LAMP-2-deficient hepatocytes, whereas that of 46-kDa mannose 6-phosphate receptor was decreased to 30% of controls due to a shorter half-life. Less receptor was found in the Golgi region and in vesicles and tubules surrounding multivesicular endosomes, suggesting impaired recycling from endosomes to the Golgi. More receptor was found in autophagic vacuoles, which may explain its shorter half-life. Our data indicate that in hepatocytes LAMP-2 deficiency either directly or indirectly leads to impaired recycling of 46-kDa mannose 6-phosphate receptors and partial mistargeting of a subset of lysosomal enzymes. Autophagic vacuoles may accumulate due to impaired capacity for lysosomal degradation."],["dc.identifier.doi","10.1091/mbc.E02-02-0114"],["dc.identifier.isi","000178268300030"],["dc.identifier.pmid","12221139"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39356"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Cell Biology"],["dc.relation.issn","1059-1524"],["dc.title","Role of LAMP-2 in lysosome biogenesis and autophagy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6539"],["dc.bibliographiccitation.issue","28"],["dc.bibliographiccitation.journal","Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","6549"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","D'Hooge, R."],["dc.contributor.author","Lullmann-Rauch, R."],["dc.contributor.author","Beckers, T."],["dc.contributor.author","Balschun, D."],["dc.contributor.author","Schwake, M."],["dc.contributor.author","Reiss, K."],["dc.contributor.author","von Figura, Kurt"],["dc.contributor.author","Saftig, P."],["dc.date.accessioned","2018-11-07T08:42:56Z"],["dc.date.available","2018-11-07T08:42:56Z"],["dc.date.issued","2005"],["dc.description.abstract","Mice with alpha-mannosidase gene inactivation provide an experimental model for alpha-mannosidosis, a lysosomal storage disease with severe neuropsychological and psychopathological complications. Neurohistological alterations in these mice were similar to those in patients and included vacuolations and axonal spheroids in the CNS and peripheral nervous system. Vacuolation was most prominent and evenly distributed in neuronal perikarya of the hippocampal CA2 and CA3 regions, whereas CA1 and dentate gyrus were weakly or not affected. Field potential recordings from CA1 region in hippocampal slices showed enhanced theta burst-induced long-term potentiation (LTP) in alpha-mannosidase-deficient mice. Longitudinal assessment in age-matched alpha-mannosidase-deficient and wild-type littermates, using an extended test battery, demonstrated a neurocognitive and psychotiform profile that may relate to the psychopathological alterations in clinical alpha-mannosidosis. Brainstem auditory-evoked potentials and basic neuromotor abilities were not impaired and did not deteriorate with age. Exploratory and conflict tests revealed consistent decreases in exploratory activity and emotional blunting in the knock-out group. alpha-Mannosidosis mice were also impaired in aversively motivated learning and acquisition of signal-shock associations. Acquisition and reversal learning in the water maze task, passive avoidance learning in the step-through procedure, as well as emotional response conditioning in an operant procedure were all impaired. Acquisition or shaping of an appetitive instrumental conditioning task was unchanged. Appetitive odor discrimination learning was only marginally impaired during shaping, whereas both the discrimination and reversal subtasks were normal. We propose that prominent storage and enhanced LTP in hippocampus have contributed to these specific behavioral alterations in alpha-mannosidase-deficient mice."],["dc.identifier.doi","10.1523/JNEUROSCI.0283-05.2005"],["dc.identifier.isi","000230478100007"],["dc.identifier.pmid","16014715"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19824"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0270-6474"],["dc.title","Neurocognitive and psychotiform behavioral alterations and enhanced hippocampal long-term potentiation in transgenic mice displaying neuropathological features of human alpha-mannosidosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]