Search results for "ADAM"
showing 10 items of 372 documents
Derecho y conciencia en Antígona: Una respuesta atemporal a los conflictos de familia
2018
El presente artículo aborda la importancia de la familia en Antígona, de Sófocles. Ante el Decreto de Creonte, por el que se prohibía, bajo pena de muerte, enterrar y llorar a Polinices, su hermana ?Antígona ? no duda en afirmar que por encima de las leyes del Estado está la ley de los dioses y la ley que dicta su conciencia, la que le exige anteponer los lazos familiares al orden público. Un acto de desobediencia civil que le conducirá a muerte.
El Fénix de Eurípides, el héroe de Anagirunte y Jerónimo de Rodas
2016
El Fénix de Eurípides y el 'tema de Putifar' Mi propósito en estas páginas es revisar algunos problemas en torno al perdido Fénix de Eurípides (TrGF v 2, frs. 803-818 Kannicht). No voy, empero, a proponer ninguna reconstrucción nueva de la obra. Existen ya una serie de tentativas en este sentido que, aunque meritorias, resultan poco concluyentes: 1 los exiguos fragmentos han sido ya explotados a fondo y probablemente no dan para más...
La unidad del pensamiento de Adam Smith como marco de comprensión de su propuesta jurídica. Una reflexión desde América latina
2019
La unidad del pensamiento de Adam Smith como marco de comprensión de su propuesta jurídica. Una reflexión desde América Latina Por Juan Camilo Salas Cardona Resumen Las inmensas riquezas que poseen América Latina y El Caribe, en lo que se refiere a sus gentes, su cultura, su biodiversidad, belleza y variedad geográfica, así como a los recursos de toda especie que provee la tierra, contrastan con la pobreza, miseria, violencia, corrupción, crisis económica, desempleo e inestabilidad política en que vive buena parte la región, desde el mal llamado descubrimiento de América, también denominado “encuentro de dos mundos”, ocurrido hace un poco más de cinco siglos. Estas circunstancias, que, con …
Quando l’amnios si rompe troppo presto e… da solo
2022
Rupture of the amniochorionic membranes is a recognized risk factor in the second and third trimester for chorioamnionitis, sepsis and preterm delivery. The isolated rupture of amnion is conversely responsible for a malformation spectrum known as early amnion rupture sequence or ADAM (Amniotic Deformity, Adhesions, Mutilations) complex, characterized by asymmetrical congenital anomalies, including limb reduction and craniofacial defects, usually arising during the 2nd or 3rd trimester of gestation. The paper reports the case of a 4-month-old infant who was referred for genetic counselling in the suspicion of malformation syndrome with asymmetrical limb reduction defects. The present case un…
Statins and the squalene synthase inhibitor zaragozic acid stimulate the non-amyloidogenic pathway of amyloid-beta protein precursor processing by su…
2010
Cholesterol-lowering drugs such as statins influence the proteolytic processing of the amyloid-beta protein precursor (AbetaPP) and are reported to stimulate the activity of alpha-secretase, the major preventive secretase of Alzheimer's disease. Statins can increase the alpha-secretase activity by their cholesterol-lowering properties as well as by impairment of isoprenoids synthesis. In the present study, we elucidate the contribution of these pathways in alpha-secretase activation. We demonstrate that zaragozic acid, a potent inhibitor of squalene synthase which blocks cholesterol synthesis but allows synthesis of isoprenoids, also stimulates alpha-secretase activity. Treatment of human n…
Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of…
2021
Abstract Brain-derived neurotrophic factor (BDNF) is an important modulator for a variety of functions in the central nervous system (CNS). A wealth of evidence, such as reduced mRNA and protein level in the brain, cerebrospinal fluid (CSF), and blood samples of Alzheimer’s disease (AD) patients implicates a crucial role of BDNF in the progression of this disease. Especially, processing and subcellular localization of BDNF and its receptors TrkB and p75 are critical determinants for survival and death in neuronal cells. Similarly, the amyloid precursor protein (APP), a key player in Alzheimer’s disease, and its cleavage fragments sAPPα and Aβ are known for their respective roles in neuropro…
Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases
2005
Cleavage of the amyloid precursor protein (APP) within the amyloid-beta (Aβ) sequence by the α-secretase prevents the formation of toxic Aβ peptides. It has been shown that the disintegrin-metalloproteinases ADAM10 and TACE (ADAM17) act as α-secretases and stimulate the generation of a soluble neuroprotective fragment of APP, APPsα. Here we demonstrate that the related APP-like protein 2 (APLP2), which has been shown to be essential for development and survival of mice, is also a substrate for both proteinases. Overexpression of either ADAM10 or TACE in HEK293 cells increased the release of neurotrophic soluble APLP2 severalfold. The strongest inhibition of APLP2 shedding in neuroblastoma c…
Constitutive and regulated α-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease
1999
Amyloid β peptide (Aβ), the principal proteinaceous component of amyloid plaques in brains of Alzheimer’s disease patients, is derived by proteolytic cleavage of the amyloid precursor protein (APP). Proteolytic cleavage of APP by a putative α-secretase within the Aβ sequence precludes the formation of the amyloidogenic peptides and leads to the release of soluble APPsα into the medium. By overexpression ofa disintegrinandmetalloprotease (ADAM), classified as ADAM 10, in HEK 293 cells, basal and protein kinase C-stimulated α-secretase activity was increased severalfold. The proteolytically activated form of ADAM 10 was localized by cell surface biotinylation in the plasma membrane, but the m…
Effect of a dominant-negative form of ADAM10 in a mouse model of Alzheimer's disease.
2009
The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid-beta protein precursor (AbetaPP) within the region of the amyloid-beta peptides to prevent their formation and aggregation in the brain. Members of the ADAM family (a disintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. We recently demonstrated that overexpression of ADAM10 in mice transgenic for human AbetaPP (ADAM10 x APP[V717I]) alleviated functional deficits related to Alzheimer's disease. To further demonstrate that this is due to the specific activity of alpha-secretase, we characterized mice overexpressing an inactive form of ADAM10 (ADAM10[E384A]; ADAM10-dn). T…
Down-regulation of Endogenous Amyloid Precursor Protein Processing due to Cellular Aging
2005
Processing of amyloid precursor protein (APP) is a well acknowledged central pathogenic mechanism in Alzheimer disease. However, influences of age-associated cellular alterations on the biochemistry of APP processing have not been studied in molecular detail so far. Here, we report that processing of endogenous APP is down-regulated during the aging of normal human fibroblasts (IMR-90). The generation of intracellular APP cleavage products C99, C83, and AICD gradually declines with increasing life span and is accompanied by a reduced secretion of soluble APP (sAPP) and sAPPalpha. Further, the maturation of APP was reduced in senescent cells, which has been shown to be directly mediated by a…