Search

Your search keyword '"Beyreuther K"' showing total 386 results
Start Over Author "Beyreuther K" Search Limiters Full Text
386 results on '"Beyreuther K"'

2. Secreted glypican binds to the amyloid precursor protein of Alzheimer's disease (APP) and inhibits APP-induced neurite outgrowth.

Author

Williamson, TG, Mok, SS, Henry, A, Cappai, R, Lander, AD, Nurcombe, V, Beyreuther, K, Masters, CL, and Small, DH

Subjects
Neurites, PC12 Cells, Animals, Mice, Rats, Alzheimer Disease, Glycosides, Heparitin Sulfate, Proteoglycans, Amyloid beta-Protein Precursor, Chromatography, Affinity, Cell Division, Heparan Sulfate Proteoglycans, Chromatography, Affinity, Biochemistry & Molecular Biology, Biological Sciences, Medical and Health Sciences, Chemical Sciences
Abstract

The amyloid precursor protein (APP) of Alzheimer's disease has been shown to stimulate neurite outgrowth in vitro. The effect of APP on neurite outgrowth can be enhanced if APP is presented to neurons in substrate-bound form, in the presence of heparan sulfate proteoglycans. To identify specific heparan sulfate proteoglycans that bind to APP, conditioned medium from neonatal mouse brain cells was subjected to affinity chromatography with recombinant APP695 as a ligand. Glypican bound strongly to the APP affinity column. Purified glypican bound to APP with an equilibrium dissociation constant of 2.8 nM and inhibited APP-induced neurite outgrowth from chick sympathetic neurons. The effect of glypican was specific for APP, as glypican did not inhibit laminin-induced neurite outgrowth. Furthermore, treatment of cultures with 4-methylumbelliferyl-beta-D-xyloside, a competitive inhibitor of proteoglycan glycanation, inhibited APP-induced neurite outgrowth but did not inhibit laminin-induced neurite outgrowth. This result suggests that endogenous proteoglycans are required for substrate-bound APP to stimulate neurite outgrowth. Secreted glypican may act to inhibit APP-induced neurite outgrowth in vivo by competing with endogenous proteoglycans for binding to APP.

Published
1996

11. Evidence that beta-amyloid protein in Alzheimer's disease is not derived by normal processing

Author

Sisodia, S.S., Koo, E.H., Beyreuther, K., Unterbeck, A., and Price, D.L.

Subjects
Glycoproteins -- Research, Protein metabolism -- Research, Protein metabolism disorders -- Research, Protein research -- Innovations -- Research, Alzheimer's disease -- Research, Science and technology, Innovations, Research
Abstract

Evidence That Β-Amyloid Protein in alzheimer's Disease Is Not Derived by Normal Processing ALZHEIMER'S DISEASE (AD), THE most common form of dementia in the elderly, affects [is greater than] 10% [...]

Published
1990

13. Simvastatin strongly reduces levels of Alzheimer's disease [Beta]-amyloid peptides A[Beta]42 and A[Beta]40 in vitro and in vivo

Author

Fassbender, K., Simons, M., Bergmann, C., Stroick, M., Lutjohann, D., Keller, P., Runz, H., Kuhl, S., Bertsch, T., von Bergmann, K., Hennerici, M., Beyreuther, K., and Hartmann, T.

Subjects
Alzheimer's disease -- Physiological aspects, Anticholesteremic agents -- Physiological aspects, Apolipoproteins -- Physiological aspects, Peptides -- Physiological aspects, Neurons -- Physiological aspects, Lipids -- Physiological aspects, Simvastatin -- Physiological aspects, Lovastatin -- Physiological aspects, Science and technology
Abstract

Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins. Moreover, elevated A[Beta]42 levels and the [Epsilon]4 allele of the lipid-carrier apolipoprotein E are regarded as risk factors for sporadic and familial Alzheimer's disease. Here we demonstrate that the widely used cholesterol-lowering drugs simvastatin and lovastatin reduce intracellular and extracellular levels of A[Beta]42 and A[Beta]40 peptides in primary cultures of hippocampal neurons and mixed cortical neurons. Likewise, guinea pigs treated with high doses of simvastatin showed a strong and reversible reduction of cerebral A[Beta]42 and A[Beta]40 levels in the cerebrospinal fluid and brain homogenate. These results suggest that lipids are playing an important role in the development of Alzheimer's disease. Lowered levels of A[Beta]42 may provide the mechanism for the observed reduced incidence of dementia in statin-treated patients and may open up avenues for therapeutic interventions.

Published
2001

15. Alzheimer's disease

Author

Masters, C. L. and Beyreuther, K.

Subjects
Alzheimer Disease, Risk Factors, Humans, Research Article, Forecasting
Published
1998

16. Subcellular trafficking of the amyloid precursor protein gene family and its pathogenic role in Alzheimer's disease

Author

Kins, S, Lauther, N, Szodorai, A, Beyreuther, K, Kins, S, Lauther, N, Szodorai, A, and Beyreuther, K

Abstract

Changes in the intracellular transport of amyloid precursor protein (APP) affect the extent to which APP is exposed to alpha- or beta-secretase in a common subcellular compartment and therefore directly influence the degree to which APP undergoes the amyloidogenic pathway leading to generation of beta-amyloid. As the presynaptic regions of neurons are thought to be the main source of beta-amyloid in the brain, attention has been focused on axonal APP trafficking. APP is transported along axons by a fast, kinesin-dependent anterograde transport mechanism. Despite the wealth of in vivo and in vitro data that have accumulated regarding the connection of APP to kinesin transport, it is not yet clear if APP is coupled to its specific motor protein via an intracellular interaction partner, such as the c-Jun N-terminal kinase-interacting protein, or by yet another unknown molecular mechanism. The cargo proteins that form a functional complex with APP are also unknown. Due to the long lifespan, and vast extent, of neurons, in particular axons, neurons are highly sensitive to changes in subcellular transport. Recent in vitro and in vivo studies have shown that variations in APP or tau affect mitochondrial and synaptic vesicle transport. Further, it was shown that this axonal dysfunction might lead to impaired synaptic plasticity, which is crucial for neuronal viability and function. Thus, changes in APP and tau expression may cause perturbed axonal transport and changes in APP processing, contributing to cognitive decline and neurodegeneration in Alzheimer's disease.

Published
2006

17. APP+ T lymphocytes selectively sorted to endomysial tubes in polymyositis displace NCAM-expressing muscle fibers

Author

Walter Schubert, Cl, Masters, and Beyreuther K

Subjects
CD8 Antigens, Cell Adhesion Molecules, Neuronal, Muscles, T-Lymphocytes, Immunohistochemistry, Polymyositis, Amyloid beta-Protein Precursor, Phenotype, Sarcolemma, Microscopy, Fluorescence, Cell Movement, T-Lymphocyte Subsets, CD4 Antigens, Microscopy, Electron, Scanning, Humans
Abstract

The characteristic pathogenic feature of polymyositis (PM) is muscle invasion by T lymphocytes penetrating the basal lamina and displacing the sarcolemma of normal muscle fibers (T cell invasion of endomysial tubes). Active forward movement of these T cells is indicated by cell extensions interdigitating with the muscle fiber surface. Here we describe for the first time high abundance of Alzheimer amyloid protein precursor (APP) in invasive T cells contacting the border of muscle fibers in PM. These are the sites of muscle fiber displacement. The percentage of APP+ T cells at these sites is significantly higher than in other neuromuscular disorders with inflammatory infiltrates suggesting a specific pathogenic function of these cells in PM. By using a new multiparameter immunofluorescence imaging procedure and confocal laser scanning microscopy, we show that APP+ T cells in PM are invasive front cells that penetrate the basal lamina of the endomysial tube and displace the muscle fiber. Mononuclear cells behind the invasive front are negative for APP or show much lower APP levels. Front T cells either express the CD8-CD4+APP+ or CD8+CD4-APP+ phenotypes, or are CD4+CD8+APP+ T cell chimeras. The highest APP concentration is found at the tip of T cell extensions interdigitating with the fiber surface. Although normal by morphological criteria, the same fibers show intense staining for the regeneration marker NCAM. This reactivity is highest at sites contacted by the APP+ T cells. The findings indicate that APP is specifically upregulated in T cells displacing muscle fibers in PM and suggest that NCAM, which may be abnormally regulated in these fibers, is a candidate molecule for interaction with APP.

Published
1993

19. Consensus meeting: monosodium glutamate – an update

Author

Beyreuther, K, primary, Biesalski, H K, additional, Fernstrom, J D, additional, Grimm, P, additional, Hammes, W P, additional, Heinemann, U, additional, Kempski, O, additional, Stehle, P, additional, Steinhart, H, additional, and Walker, R, additional

Published
2006
Full Text
View/download PDF

20. Ultrastructural localization of the putative precursors of the A4 amyloid protein associated with Alzheimer's disease

Author

Catteruccia, N, WILLINGALE-THEUNE, J, Bunke, D, Prior, R, Masters, Cl, Crisanti, A., and Beyreuther, K.

Subjects
Mice, Mice, Inbred BALB C, Serum Amyloid A Protein, Alzheimer Disease, Pituitary Gland, Anterior, Muscles, Animals, Antibodies, Monoclonal, Humans, Protein Precursors, Cytoplasmic Granules, Salivary Glands, Research Article
Abstract

Any explanation of the causes of Alzheimer's disease and of its unique cerebral pathologic features must take into account the distribution and ultrastructural localization of the pre-A4 amyloid proteins in tissues and organs. The authors have analyzed the expression of the pre-A4 amyloid proteins in several tissues by immunogold electron microscopy and by immunofluorescence. For this purpose, they have used a mouse monoclonal antibody and a guinea pig antiserum raised against two synthetic peptides corresponding to two different sequences common to all the full-length forms of the A4 amyloid precursors. They observed a tissue-specific distribution of the secreted and the transmembrane form of the precursors. The authors could determine that the secreted form is generated in vivo within the cytoplasm. In the salivary glands and in the adenohypophysis, all the immunoreactivity is associated with the process of secretion, whereas in the muscle, a staining pattern compatible with the presence of the pre-A4 amyloid proteins in the sarcoplasmic reticulum has been observed. This difference in the localization may reflect tissue-specific processing pathways and suggests that posttranslational modifications such as proteolytic removal of the transmembrane and cytoplasmic domains contribute to the structural and thus functional diversity of the A4 amyloid precursors.

Published
1990

21. Identifikation des Glykosylphosphatidylinositol-verankerten Heparan Sulfat Proteoglykans Glypikan als Toxizitäts-vermittelndem Rezeptor für Beta-Amyloid der Alzheimer´schen Krankheit in der neuronalen PC12 Zellinie

Author

Henn, F. A., Beyreuther, K., Einhäupl, Karl Max, Schulz, Joachim Günther, Henn, F. A., Beyreuther, K., Einhäupl, Karl Max, and Schulz, Joachim Günther

Abstract

In der vorliegenden Arbeit konnte mit der PC12 Zellinie und dem MTT Viabilitätsassay Glypikan, ein Glykosylphosphatidylinositol-verankertes Heparan Sulfat, als Rezeptor identifiziert werden, der die toxischen Effekte von [beta]-Amyloid vermittelt. Kompetitive Substanzen im Medium, enzymatische Behandlung der Zelloberfläche und Block spezifischer zellulärer Synthesewege wurden eingesetzt. [beta]-Amyloid wird eine zentrale Rolle in der Pathogenese der Alzheimer'schen Krankheit zugeschrieben. Eine Intervention auf Ebene der [beta]-Amyloid-Rezeptor Interaktion könnte einen Therapieansatz für die Alzheimer'sche Krankheit darstellen. Weitere Experimente sind notwendig, um die Rolle von Glypikan bei der Vermittlung der [beta]-Amyloid Toxizität im Alzheimer-Gehirn zu untersuchen, z.B. in der Primärkultur von Neuronen und Mikroglia oder im lebenden Hirnschnitt. Eine ähnliche anatomische Verteilung der Glypikanexpression im Rattenhirn und der neurofibrillären Bündel im Alzheimergehirn wurde gefunden. Eine mögliche Rolle für Glypikan bei der Entstehung der neurofibrillären Bündel muß im Autopsiegehirn von Alzheimerpatienten überprüft werden., [beta]-amyloid is thought to play a major role in the pathogenesis of Alzheimer's disease. In PC12 cell culture, competitive substances in cell culture medium, enzymatic cell surface treatment und block of specific cell synthesis pathways were used to identify glypican, a GPI- anchored heparan sulfate proteoglycan, as a receptor that mediates the toxic effects of [beta]-amyloid.

Published
1998

25. Transgenic Mice Expressing Human App Derived Transgenes

Author

UCL - MD/FSIO - Département de physiologie et pharmacologie, Theisen, M., Czech, C., Macq, AF., Delaère, P, Monning, U., Tremp, G., Mercken, L., Perraud, F., Alihadji, D., Mischler, F., Paliga, K., Baron, H., Lepecq, JB., Pavirani, A., Octave, Jean-Noël, Beyreuther, K., The Fourth International Conference on Alzheimer's Disease and Related Disorders, UCL - MD/FSIO - Département de physiologie et pharmacologie, Theisen, M., Czech, C., Macq, AF., Delaère, P, Monning, U., Tremp, G., Mercken, L., Perraud, F., Alihadji, D., Mischler, F., Paliga, K., Baron, H., Lepecq, JB., Pavirani, A., Octave, Jean-Noël, Beyreuther, K., and The Fourth International Conference on Alzheimer's Disease and Related Disorders

Abstract

of the Transgenic Mice Expressing Human App Derived Transgenes

Published
1994

49. Identification of structural variations in the carboxyl terminus of Alzheimer's disease-associated βA4[1–42] amyloid using a monoclonal antibody.

Author

Jayasena, U. L. H. R., Gribble, S. K., Mckenzie, A., Beyreuther, K., Masters, C. L., and Underwood, J. R.

Subjects
ALZHEIMER'S disease, AMINO acids, EPITOPES, NITROCELLULOSE
Abstract

The accumulation of amyloid plaques and amyloid congophilic angiopathy (ACA) in the brains of affected individuals is one of the main pathological features of Alzheimer's disease. Within these deposits, the βA4 (Aß) polypeptide represents a major component with the C-terminal 39–43 amino acid variants being most abundant. Using a mouse IgG1 MoAb produced by hybridoma βA4[35–43]-95.2 3B9, which reacts with the epitope is defined by the amino acid residues βA438[GVV]40, this study has identified a unique conformation within the carboxyl terminus of human βA4[1–42]. Although the βA438[GVV]40 sequence is present within the C-termini of human βA4[1–40] and βA4[1–43] and the βA4-containing region of human APP, the βA4[35–43]-95.2 3B9 MoAb (designated MoAb 3B9) does not bind these polypeptides, demonstrating a high degree of specificity for the βA438[GVV]40 epitope as presented within the βA4[1–42] sequence. The βA4[1–42] epitope bound by MoAb 3B9 is sensitive to heating (100°C for 5 min) and is denatured by SDS but not by oxidative radio-iodination of βA4 or by adsorption to plastic surfaces or nitrocellulose. The recognition of βA4 plaque deposits and ACA by MoAb 3B9 within formalin-fixed sections of human AD brain demonstrates the potential of these antibodies for investigating the role of the unique βA4[1–42] conformation in the development of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Published
2001
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results