Search results for "M10"

A Closer Look at α-Secretase

2008

Accumulation of amyloid beta-peptides (Abeta) in the brain is believed to contribute to the development of Alzheimer disease (AD). Abeta, a 40-42 amino acid-comprising proteolytical fragment of the amyloid precursor protein (APP), is released from APP by sequential cleavages via beta- and gamma-secretases. However, the predominant route of APP processing consists of successive cleavages by alpha- and gamma-secretases. Alpha-secretase attacks APP inside the Abeta sequence, and therefore prevents formation of neurotoxic Abeta. After cleavage by alpha-secretase, the soluble N-terminal domain of APP, which possesses neurotrophic and neuroprotective properties, is released. In AD patients, a dec…

The metalloproteinase-disintegrin ADAM10 is exclusively expressed by type I muscle fibers.

2008

ADAM10 (Kuzbanian) is a member of a recently discovered family of membrane-anchored metalloproteinases with a complex and conserved domain structure. In part, these metalloproteinases have been implicated in muscle formation. Herein the expression pattern of ADAM10 in human skeletal muscle was studied. ADAM10 was found to be present in human myoblasts and to be exclusively expressed in type I fibers, suggesting that it may be critical in muscle fiber differentiation.

A more cost-effective geomatic approach to modelling PM10 dispersion across Europe

2014

International audience; PM10 concentrations in most major European cities exceed the limits set by the European Directive and are expected to continue to do so in the coming years. Moreover, PM10s can be transported over long distances impacting air quality, public health and ecosystem functionality far from their sources of emission. Modelling remains one of the only options for tracking PM10 deposition in remote areas with no monitoring stations. Even so, air pollution models based on atmospheric physics usually imply substantial economic, logistical and computational investment. In this work, we present a new geomatic approach to modelling mean annual PM10 concentrations across Europe. O…

Influence of ADAM10 on prion protein processing and scrapie infectiosity in vivo.

2009

Abstract Both the cellular prion protein (PrPc) and the amyloid precursor protein (APP) are physiologically subjected to complex proteolytic processing events. While for APP the proteinases involved – alpha-, beta- and gamma-secretase – have been identified in vitro and in vivo, the cleavage of PrPc by now has been linked only to the shedding activity of the metalloproteinase ADAM10 and/or ADAM17 in cell culture. Here we show that neuronal overexpression of the alpha-secretase ADAM10 in mice reduces all PrPc species detected in the brain instead of leading to enhanced amounts of specific cleavage products of PrPc. Additionally, the incubation time of mice after scrapie infection is signific…

LC–MS Based Cleavage Site Profiling of the Proteases ADAM10 and ADAM17 Using Proteome-Derived Peptide Libraries

2014

A Disintegrin and Metalloproteinase 10 (ADAM10) and ADAM17 catalyze ectodomain shedding of a number of cell surface proteins important for embryonic development and tissue homeostasis. Changes in the expression levels or dysregulated proteolytic activity of ADAM10 and ADAM17 have been shown to play important roles in multiple diseases such as inflammation, cancer, and neurodegenerative disorders. Despite the well documented substrate repertoire of ADAM10 and ADAM17, little is known about their cleavage site specificity. We optimized Q-PICS (Quantitative Proteomics for the Identification of Cleavage Sites) to elucidate the cleavage site specificity of recombinant murine ADAM10 and ADAM17. Tw…

The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10

2012

The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin α and β we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleavage fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)—the constitutive α-secretase—is activated by meprin β through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincubation with meprin…

P2‐307: A stable G‐quadruplex within the ADAM10 5'‐UTR is involved in translational repression of ADAM10

2011

Expecting the unexpected: Quantifying the persistence of unexpected hypersurfaces

2021

If $X \subset \mathbb P^n$ is a reduced subscheme, we say that $X$ admits an unexpected hypersurface of degree $t$ for multiplicity $m$ if the imposition of having multiplicity $m$ at a general point $P$ fails to impose the expected number of conditions on the linear system of hypersurfaces of degree $t$ containing $X$. Conditions which either guarantee the occurrence of unexpected hypersurfaces, or which ensure that they cannot occur, are not well understand. We introduce new methods for studying unexpectedness, such as the use of generic initial ideals and partial elimination ideals to clarify when it can and when it cannot occur. We also exhibit algebraic and geometric properties of $X$ …

Alcadein cleavages by amyloid beta-precursor protein (APP) alpha- and gamma-secretases generate small peptides, p3-Alcs, indicating Alzheimer disease…

2009

Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins, designated Alc(alpha), Alc(beta), and Alc(gamma). The Alcs express in neurons dominantly and largely colocalize with the Alzheimer amyloid precursor protein (APP) in the brain. Alcs and APP show an identical function as a cargo receptor of kinesin-1. Moreover, proteolytic processing of Alc proteins appears highly similar to that of APP. We found that APP alpha-secretases ADAM 10 and ADAM 17 primarily cleave Alc proteins and trigger the subsequent secondary intramembranous cleavage of Alc C-terminal fragments by a presenilin-dependent gamma-secretase complex, thereby generating "APP p3-like" and non-aggregative Alc pe…

2014

In the pathogenesis of Alzheimer’s disease (AD) the homeostasis of amyloid precursor protein (APP) processing in the brain is impaired. The expression of the competing proteases ADAM10 (a disintegrin and metalloproteinase 10) and BACE-1 (beta site APP cleaving enzyme 1) is shifted in favor of the A-beta generating enzyme BACE-1. Acitretin–a synthetic retinoid–e.g., has been shown to increase ADAM10 gene expression, resulting in a decreased level of A-beta peptides within the brain of AD model mice and thus is of possible value for AD therapy. A striking challenge in evaluating novel therapeutically applicable drugs is the analysis of their potential to overcome the blood-brain barrier (BBB)…