ABSTRACT
Heterogeneous single-site catalysts consist of isolated, well-defined, active sites that are spatially separated in a given solid and, ideally, structurally identical. In this review, the potential of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) as platforms for the development of heterogeneous single-site catalysts is reviewed thoroughly. In the first part of this article, synthetic strategies and progress in the implementation of such sites in these two classes of materials are discussed. Because these solids are excellent playgrounds to allow a better understanding of catalytic functions, we highlight the most important recent advances in the modelling and spectroscopic characterization of single-site catalysts based on these materials. Finally, we discuss the potential of MOFs as materials in which several single-site catalytic functions can be combined within one framework along with their potential as powerful enzyme-mimicking materials. The review is wrapped up with our personal vision on future research directions.
ABSTRACT
Introducción: Existe un creciente interés en las nuevas estrategias terapéuticas para la enfermedad de Alzheimer (EA) orientadas a reducir la carga de péptido β-amiloide (Aβ) en el cerebro mediante el secuestro de Aβ en el plasma, un alto porcentaje del cual se encuentra unido a albúmina y otras proteínas plasmáticas. En esta revisión, se analizan los conceptos de interacción entre Aβ y albúmina que han conducido al desarrollo del proyecto AMBAR (Alzheimer Management By Albumin Replacement), un nuevo estudio clínico multicéntrico, aleatorizado y controlado para el tratamiento de la EA. Desarrollo: Resultados de estudios de investigación básica indican que Albutein(R) (albúmina terapéutica, Grifols) contiene niveles no cuantificables de Aβ. Asimismo demuestran la capacidad de Albutein(R) de unirse a Aβ. Por otro lado, en la EA existe un elevado estrés nitro-oxidativo asociado a los agregados fibrilares de Aβ que puede inducir la modificación de la albúmina, afectando a sus funciones biológicas. Resultados del estudio en fase II confirman que el reemplazo de la albúmina endógena con Albutein(R) 5% mediante aféresis terapéutica es factible y seguro en pacientes con EA, produciendo una movilización de Aβ, además de una mejoría cognitiva de los pacientes tratados. En el estudio AMBAR se ensayará el uso combinado de aféresis terapéutica y hemoféresis con el posible efecto potenciador de Albutein(R) con reposición de inmunoglobulina por vía intravenosa (Flebogamma ® DIF). Se evaluarán los cambios cognitivos, funcionales y conductuales en pacientes con EA leve o moderada. Conclusiones: El estudio AMBAR representa una nueva perspectiva terapéutica ante la EA
Introduction: There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (Aβ) burden in the brain by sequestering plasma Aβ, a large proportion of which is bound to albumin and other proteins. This review discusses the concepts of interaction between Aβ and albumin that have given rise to AMBAR (Alzheimer's Disease Management by Albumin Replacement) project, a new multicentre, randomised, controlled clinical trial for the treatment of AD. Development: Results from preliminary research suggest that Albutein(R) (therapeutic albumin, Grifols) contains no quantifiable levels of Aβ. Studies also show that Albutein(R) has Aβ binding capacity. On the other hand, AD entails a high level of nitro-oxidative stress associated with fibrillar aggregates of Aβ that can induce albumin modification, thus affecting its biological functions. Results from the phase II study confirm that using therapeutic apheresis to replace endogenous albumin with Albutein(R) 5% is feasible and safe in patients with AD. This process resulted in mobilisation of Aβ and cognitive improvement in treated patients. The AMBAR study will test combination therapy with therapeutic apheresis and haemopheresis with the possible leverage effect of Albutein(R) with intravenous immunoglobulin replacement (Flebogamma® DIF). Cognitive, functional, and behavioural changes in patients with mild to moderate AD will be assessed. Conclusions: the AMBAR study represents a new therapeutic perspective for AD
Subject(s)
Humans , Male , Female , Alzheimer Disease/therapy , Blood Component Removal/instrumentation , Blood Component Removal/methods , Albumins/therapeutic use , Immunoglobulins/therapeutic use , Enzyme-Linked Immunosorbent Assay/instrumentation , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent AssayABSTRACT
The gate-opening phenomenon in ZIFs is of paramount importance to understand their behavior in industrial molecular separations. Here we show for the first time using in situ inelastic neutron scattering (INS) the swinging of the -CH3 groups and the imidazolate linkers in the prototypical ZIF-8 and ZIF-8@AC hybrid materials upon exposure to mild N2 pressure.
ABSTRACT
INTRODUCTION: There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (Aß) burden in the brain by sequestering plasma Aß, a large proportion of which is bound to albumin and other proteins. This review discusses the concepts of interaction between Aß and albumin that have given rise to AMBAR (Alzheimer's Disease Management by Albumin Replacement) project, a new multicentre, randomised, controlled clinical trial for the treatment of AD. DEVELOPMENT: Results from preliminary research suggest that Albutein(®) (therapeutic albumin, Grifols) contains no quantifiable levels of Aß. Studies also show that Albutein(®) has Aß binding capacity. On the other hand, AD entails a high level of nitro-oxidative stress associated with fibrillar aggregates of Aß that can induce albumin modification, thus affecting its biological functions. Results from the phase ii study confirm that using therapeutic apheresis to replace endogenous albumin with Albutein(®) 5% is feasible and safe in patients with AD. This process resulted in mobilisation of Aß and cognitive improvement in treated patients. The AMBAR study will test combination therapy with therapeutic apheresis and haemopheresis with the possible leverage effect of Albutein(®) with intravenous immunoglobulin replacement (Flebogamma(®) DIF). Cognitive, functional, and behavioural changes in patients with mild to moderate AD will be assessed. CONCLUSIONS: the AMBAR study represents a new therapeutic perspective for AD.
Subject(s)
Albumins/isolation & purification , Albumins/therapeutic use , Alzheimer Disease/therapy , Immunoglobulins, Intravenous/therapeutic use , Plasma Exchange/methods , Plasmapheresis/methods , Aged , Aged, 80 and over , Albumins/chemistry , Amyloid beta-Peptides/metabolism , Humans , Protein BindingABSTRACT
One of the main concerns in the technological application of several metal-organic frameworks (MOFs) relates to their structural instability under pressure (after a conforming step). Here we report for the first time that mechanical instability can be highly improved via nucleation and growth of MOF nanocrystals in the confined nanospace of activated carbons.
Subject(s)
Carbon/chemistry , Nanoparticles/chemistry , Organometallic Compounds/chemistry , Metal-Organic Frameworks , Molecular StructureABSTRACT
Alzheimer's disease (AD), the most prevalent neurodegenerative disease worldwide, has two main hallmarks: extracellular deposits of amyloid ß-peptide (Aß) and intracellular neurofibrillary tangles composed by tau protein. Most AD cases are sporadic and are not dependent on known genetic causes; aging is the major risk factor for AD. Therefore, the oxidative stress has been proposed to initiate the uncontrolled increase in Aß production and also to mediate the Aß's deleterious effects on brain cells, especially on neurons from the cortex and hippocampus. The production of free radicals in the presence of nitric oxide (NO) yields to the peroxynitrite generation, a very reactive agent that nitrotyrosinates the proteins irreversibly. The nitrotyrosination produces a loss of protein physiological functions, contributing to accelerate AD progression. One of the most nitrotyrosinated proteins in AD is the enzyme triosephosphate isomerase (TPI) that isomerises trioses, regulating glucose consumption by both phosphate pentose and glycolytic pathways and thereby pyruvate production. Hence, any disturbance in the glucose supply could affect the proper brain function, considering that the brain has a high rate of glucose consumption. Besides this directly affecting to the energetic metabolism of the neurons, TPI modifications, such as mutation or nitrotyrosination, increase methylglyoxal production, a toxic precursor of advanced glycated end-products (AGEs) and responsible for protein glycation. Moreover, nitro-TPI aggregates interact with tau protein inducing the intraneuronal aggregation of tau. Here we review the relationship between modified TPI and AD, highlighting the relevance of this protein in AD pathology and the consequences of protein nitro-oxidative modifications.
