RESUMEN
The accumulation of the amyloid-beta peptide (Abeta) continues to emerge as a central factor in Alzheimer's disease (AD). In recent years attention has been drawn to clearance mechanisms of Abeta as evidence suggests reduced clearance may be linked to late-onset AD. Direct degradation of Abeta by endopeptidases has emerged as one critical pathway of clearance. Of particular interest are endopeptidases that are sensitive to the neprilysin inhibitors thiorphan and phosphoramidon (i.e. "NEP-like") as these inhibitors induce a dramatic increase in Abeta levels resulting in rapid plaque formation in wild-type rodents. This review focuses on neprilysin (NEP) and on another NEP-like endopeptidase termed neprilysin-2 (NEP2). The involvement of these endopeptidases in AD and the state of their therapeutic development are discussed.
Asunto(s)
Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/terapia , Precursor de Proteína beta-Amiloide/metabolismo , Endopeptidasas/metabolismo , Terapia Genética/métodos , Neprilisina/metabolismo , Encéfalo/enzimología , Encéfalo/fisiopatología , Endopeptidasas/genética , Regulación Enzimológica de la Expresión Génica/genética , Terapia Genética/efectos adversos , Humanos , Neprilisina/genética , Péptidos/farmacología , Péptidos/uso terapéutico , Regulación hacia Arriba/genéticaRESUMEN
We present a theory for the shape, size, and nonuniform composition profile of a small prepyramid island in an alloy epitaxial film when surface diffusion is much faster than deposition and bulk diffusion. The predicted composition profile has segregation of the larger misfit component to the island peak, with segregation enhanced by misfit strain and solute strain but retarded by alloy solution thermodynamics. Vertical composition gradients through the center of the island due to this mechanism are on the order of 2%/nm for Ge(X)Si(1-X)/Si and 10-15%/nm for In(X)Ga(1-X)As/GaAs.
RESUMEN
The initial stages of the formation of SiGe islands on Si(001) pose a long-standing puzzle. We show that the behavior can be consistently explained by one simple assumption-that for strained SiGe, (001) is a stable orientation but not a facet orientation. Calculations of energy and morphology reproduce the key features of "prepyramid" and "pyramid" islands, and explain the initial formation and subsequent shape transition. Scanning tunneling microscopy measurements confirm the key assumptions and predictions of the model.
RESUMEN
Charged carboxymethyl-beta-cyclodextrin was successful in the capillary electrophoretic separation of a series of tricyclic antidepressants. The cyclodextrin alone was successful in the separation of carbamazepine, protriptyline, desipramine, clomipramine, and opipramol using a 3-(trimethoxysilyl)propyl methacrylate capillary coating to reduce the electroosmotic flow. The ideal buffer pH was found to be in the range of 6-7 and the ideal cyclodextrin concentration to be 10 mM. All nine antidepressants were resolved using the charged cyclodextrin in the micellar electrokinetic chromatography (MEKC) mode with sodium dodecyl sulfate as the surfactant. Neither the cyclodextrin nor the surfactant alone were successful in resolving the whole series of compounds under investigation but a combination of both produced the separation. Separations were performed on a linear polyacrylamide coated capillary. The ideal pH of the buffer was in the range of 5-7.