Search results for "M10"

A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model

2004

Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (A beta peptides) in the brain. In the nonamyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by the alpha-secretase within the A beta peptide sequence. Proteinases of the ADAM family (adisintegrin and metalloproteinase) are the main candidates as physiologically relevant alpha-secretases, but early lethality of knockout animals prevented a detailed analysis in neuronal cells. To overcome this restriction, we have generated transgenic mice that overexpress either ADAM10 or a catalytically inactive ADAM10 mutant. In this report we show that a moderate neuronal overexpression of ADAM10 i…

Over-expression of two different forms of the α-secretase ADAM10 affects learning and memory in mice

2006

Members of the ADAM family (adisintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the region of the Abeta peptides preventing their aggregation in the brain. The increase of alpha-secretase activity in the brain provides a plausible strategy to prevent Abeta formation. Concerning this possibility two transgenic mouse lines (FVB/N) have been created: mice over-expressing the bovine form of the alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha-secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1 ge…

Effects of neuron-specific ADAM10 modulation in an in vivo model of acute excitotoxic stress.

2008

A disintegrin and metalloprotease (ADAM) 10 is the main candidate enzyme for the alpha-secretase processing of the amyloid precursor protein (APP). Neuron-specific ADAM10 overexpression proved beneficial in the APP[V717I] mutant Alzheimer mouse model [Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113:1456-1464]. Since Alzheimer patients have a high prevalence for epileptic seizures, we investigated the effects of ADAM10 modula…

Rational normal curves and Hadamard products

2021

AbstractGiven $$r>n$$ r > n general hyperplanes in $$\mathbb P^n,$$ P n , a star configuration of points is the set of all the n-wise intersection of the hyperplanes. We introduce contact star configurations, which are star configurations where all the hyperplanes are osculating to the same rational normal curve. In this paper, we find a relation between this construction and Hadamard products of linear varieties. Moreover, we study the union of contact star configurations on a same conic in $$\mathbb P^2$$ P 2 , we prove that the union of two contact star configurations has a special h-vector and, in some cases, this is a complete intersection.

ANÁLISIS DE LOS HOTELES DE ALTA CATEGORÍA DE CROACIA DESDE EL ENFOQUE HOTEL-HUÉSPED

2011

RESUMENCroacia viene experimentando un auge turístico notable en los últimos diez años. Es crucial para su futuro desarrollo saber gestionar el sector hotelero de acuerdo con las nuevas exigencias del mercado. Este trabajo pretende analizar los hoteles de alta categoría de Croacia desde un doble enfoque hotel-huésped, centrándose en una nueva estrategia de marketing denominada Comunicación Integrada de Marketing (CIM), los avances en las Tecnologías de Información y Comunicación (TIC) y la lealtad. Los resultados demuestran el elevado grado de implantación de las TIC y de la CIM y el grado moderado de los programas de lealtad en los hoteles analizados. Además, confirman la influencia de las…

Strongly decelerated expansion of SN 1979C

2002

We observed SN1979C in M100 on 4 June 1999, about twenty years after explosion, with a very sensitive four-antenna VLBI array at the wavelength of 18cm. The distance to M100 and the expansion velocities are such that the supernova cannot be fully resolved by our Earth-wide array. Model-dependent sizes for the source have been determined and compared with previous results. We conclude that the supernova shock was initially in free expansion for 6 +/- 2 yrs and then experienced a very strong deceleration. The onset of deceleration took place a few years before the abrupt trend change in the integrated radio flux density curves. We estimate the shocked swept-up mass to be about 1.6 solar masse…

Eléments d'économie managériale

1989

Melittin Modulates Keratinocyte Function through P2 Receptor-dependent ADAM Activation

2012

Melittin, the major component of the bee venom, is an amphipathic, cationic peptide with a wide spectrum of biological properties that is being considered as an anti-inflammatory and anti-cancer agent. It modulates multiple cellular functions but the underlying mechanisms are not clearly understood. Here, we report that melittin activates disintegrin-like metalloproteases (ADAMs) and that downstream events likely contribute to the biological effects evoked by the peptide. Melittin stimulated the proteolysis of ADAM10 and ADAM17 substrates in human neutrophil granulocytes, endothelial cells and murine fibroblasts. In human HaCaT keratinocytes, melittin induced shedding of the adhesion molecu…

Unsaturated Fatty Acids Drive Disintegrin and Metalloproteinase (ADAM)-dependent Cell Adhesion, Proliferation, and Migration by Modulating Membrane F…

2011

The disintegrin-metalloproteinases ADAM10 and ADAM17 mediate the release of several cell signaling molecules and cell adhesion molecules such as vascular endothelial cadherin or L-selectin affecting endothelial permeability and leukocyte transmigration. Dysregulation of ADAM activity may contribute to the pathogenesis of vascular diseases, but the mechanisms underlying the control of ADAM functions are still incompletely understood. Atherosclerosis is characterized by lipid plaque formation and local accumulation of unsaturated free fatty acids (FFA). Here, we show that unsaturated FFA increase ADAM-mediated substrate cleavage. We demonstrate that these alterations are not due to genuine ch…

Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression

2015

Abstract Background Alzheimer's disease represents one of the main neurological disorders in the aging population. Treatment options so far are only of symptomatic nature and efforts in developing disease modifying drugs by targeting amyloid beta peptide-generating enzymes remain fruitless in the majority of human studies. During the last years, an alternative approach emerged to target the physiological alpha-secretase ADAM10, which is not only able to prevent formation of toxic amyloid beta peptides but also provides a neuroprotective fragment of the amyloid precursor protein – sAPPalpha. Purpose To identify novel alpha-secretase enhancers from a library of 313 extracts of medicinal plant…