Search results for "M1"

Alpha-secretase activation--an approach to Alzheimer's disease therapy.

2006

The nonamyloidogenic pathway of processing the amyloid precursor protein (APP) involves the cleavage within the amyloid-beta peptide sequence, and thus precludes amyloid-beta formation. The identification of a member of the disintegrin and metalloproteinase family, ADAM10, as an alpha-secretase that prevents plaque formation and hippocampal deficits in vivo gave us the possibility to examine the alpha-secretase as a potential target for the therapy of Alzheimer's disease. Within the priority program Cellular Mechanisms of Alzheimer's Disease, we investigated several approaches to stimulate the alpha-secretase pathway. Two protein convertases were found to be responsible for the removal of t…

The Role of the anti-amyloidogenic secretase ADAM10 in shedding the APP-like proteins.

2011

ADAM10 (A disintegrin and metalloproteinase 10) has been demonstrated as an enzyme with protective properties in Alzheimer's disease: in mouse models it not only lowered generation of toxic A-beta peptides and formation of senile plaques but also alleviated learning deficits and enhanced synaptic density. This is due to cleavage of the amyloid precursor protein (APP) within its A-beta stretch and to the release of the extracellular domain of APP with neuroprotective function. Aside from cleaving APP, ADAM10 has been linked to over 40 putative substrates at least in cell culture. These substrates are connected with important cellular functions such as cell migration, stress response and tran…

The Non-Amyloidogenic Pathway: Structure and Function of α-Secretases

2006

The amyloid cascade hypothesis is the most accepted explanation for the pathogenesis of Alzheimer’s disease (AD). APP is the precursor of the amyloid β peptide (Aβ), the principal proteinaceous component of amyloid plaques in brains of Alzheimer’s disease patients. Proteolytic cleavage of APP by the α-secretase within the Aβ sequence precludes formation of amyloidogenic peptides and leads to a release of soluble APPsα which has neuroprotective properties. In several studies, a decreased amount of APPsα in the cerebrospinal fluid of AD patients has been observed. Three members of the ADAM family (a disintegrin and metalloproteinase) ADAM-10, ADAM-17 (TACE) and ADAM-9 have been proposed as α-…

THE EFFECTS OF MUSCARINIC AGONISTS AND ANTAGONISTS ON ACETYLCHOLINE RELEASE FROM PERIPHERAL CHOLINERGIC NERVES IN THE ABSENCE AND PRESENCE OF A CHOLI…

1980

Is it the time of seno-therapeutics application in cardiovascular pathological conditions related to ageing?

2021

It rates that in 2030, the cardiovascular diseases (CVD) will result in 40% of all deaths and rank as the leading cause. Thus, the research of appropriate therapies able to delay or retard their onset and progression is growing. Of particular interest is a new branch of the medical science, called anti-ageing medicine since CVD are the result of cardiovascular ageing. Senescent cells (SC) accumulate in cardiovascular system contributing to the onset of typical age-related cardiovascular conditions (i.e., atherosclerosis, medial aorta degeneration, vascular remodeling, stiffness). Such conditions progress in cardiovascular pathologies (i.e., heart failure, coronary artery disease, myocardial…

Docetaxel-Loaded Nanoparticles Assembled from β-Cyclodextrin/Calixarene Giant Surfactants: Physicochemical Properties and Cytotoxic Effect in Prostat…

2017

Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics …

The role of intellectual capital and entrepreneurial characteristics as innovation drivers

2014

La innovacion y la iniciativa empresarial son estrategias organizacionales esenciales para encontrar una salida a la crisis mundial que afecta a las empresas de hoy en dia. Por lo tanto, el estudio de como los factores organizacionales como el capital intelectual o las caracteristicas de los empresarios afectan el exito de un proyecto empresarial innovador, es de gran importancia para ayudar a las organizaciones actuales a encontrar una solucion a este problema. El capital intelectual implica una inversion en capital humano, estructural y relacional. Por consiguiente, nuestro objetivo investigativo se centra en analizar la influencia del capital intelectual asi como las caracteristicas pers…

Caracterización de las aguas residuales y calibración del modelo matemático BNRM1 para la simulación de los procesos de eliminación biológica de mate…

2009

La necesidad de profundizar en el conocimiento del proceso de depuración biológica de las aguas residuales, para la eliminación de materia orgánica y nutrientes, ha conducido a la formulación de modelos matemáticos que permitan reproducir el comportamiento del sistema. En este sentido, el grupo de investigación CALAGUA ha desarrollado el modelo BNRM1, el cual considera no sólo la actividad de las bacterias heterótrofas, autótrofas y acumuladoras de fósforo sino que además tiene en cuenta la actividad de microorganismos fermentativos en el proceso de fangos activados, como las bacterias acidogénicas. En este trabajo se ha propuesto como objetivo principal lograr una adecuada simulación del f…

Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

2014

Mucoadhesive polymers in pharmaceutical formulations release drugs in mucosal areas. They interact and fix to mucus via molecular interpenetration, etc ., which increase drug bioavailability. Polymers physicochemical properties affect formulation mucoadhesion, rheological behaviour and drug absorption. Hyaluronan (HA) is selected as a mucoadhesive and biodegradable polymer. Geometric, topological and fractal analyses are carried out with program TOPO. Reference calculations are performed with algorithm GEPOL. Procedure TOPO underestimates molecular volume by 0.7%. Error results 5% in surface area and derived topological indices. Solvent-accessible surface is undercalculated by 3%: from hexa…

Detoxication Strategy of Epoxide Hydrolase—The Basis for a Novel Threshold for Definable Genotoxic Carcinogens

2004

From our recent work on the three-dimensional structure of epoxide hydrolases we theoretically deduced the likelihood of a two-step catalytic mechanism that we and others have subsequently experimentally confirmed. Analysis of the rate of the two steps by us and by others show that the first step—responsible for removal of the reactive epoxide from the system—works extraordinarily fast (typically three orders of magnitude faster than the second step), sucking up the epoxide like a sponge. Regeneration of the free enzyme (the second step of the catalytic mechanism) is slow. This becomes a toxicological problem only at doses of the epoxide that titrate the enzyme out. Our genotoxicity work s…