RESUMEN
Polyphenols are a large group of phytonutrients found in herbal beverages and foods. They have manifold biological activities, including antioxidative, antimicrobial, and anti-inflammatory properties. Interestingly, some polyphenols bind to amyloid and substantially ameliorate amyloid diseases. Misfolding, aggregation, and accumulation of amyloid fibrils in tissues or organs leads to a group of disorders, called amyloidoses. Prominent diseases are Alzheimer's, Parkinson's, and Huntington's disease, but there are other, less well-known diseases wherein accumulation of misfolded protein is a prominent feature. Amyloidoses are a major burden to public health. In particular, Alzheimer's disease shows a strong increase in patient numbers. Accelerated development of effective therapies for amyloidoses is a necessity. A viable strategy can be the prevention or reduction of protein misfolding, thus reducing amyloid build-up by restoring the cellular aggretome. Amyloid-binding polyphenols affect amyloid formation on various levels, e.g. by inhibiting fibril formation or steering oligomer formation into unstructured, nontoxic pathways. Consequently, preclinical studies demonstrate reduction of amyloid-formation by polyphenols. Amyloid-binding polyphenols might be suitable lead structures for development of imaging agents for early detection of disease and monitoring amyloid deposition. Intake of dietary polyphenols might be relevant to the prevention of amyloidoses. Nutraceutical strategies might be a way to reduce amyloid diseases.
Asunto(s)
Amiloide/metabolismo , Amiloidosis/tratamiento farmacológico , Polifenoles/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Amiloide/química , Animales , Modelos Animales de Enfermedad , Humanos , Fitoquímicos/farmacologíaRESUMEN
Alzheimer's disease (AD) is a severe neurodegenerative disorder without curative treatment. Extensive data on pathological molecular processes have been accumulated over the last years. These data combined allows a systems biology approach to identify key regulatory elements of AD and to establish a model descriptive of the disease process which can be used for the development of therapeutic agents. In this study, the authors propose a closed network that uses a set of nodes (amyloid beta, tau, beta-secretase, glutamate, cyclin-dependent kinase 5, phosphoinositide 3-kinase and hypoxia-induced factor 1 alpha) as key elements of importance to the pathogenesis of AD. The proposed network, in total 39 nodes, is able to become a novel tool capable of providing new insights into AD, such as feedback loops. Further, it highlights interconnections between pathways and identifies their combination for therapy of AD.
Asunto(s)
Algoritmos , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Modelos Neurológicos , Proteínas del Tejido Nervioso/metabolismo , Transducción de Señal , Simulación por Computador , HumanosRESUMEN
Polyphenols are a broad class of compounds. Some are ingested in substantial quantities from nutritional sources, more are produced by medicinal plants, and some of them are taken as drugs. It is becoming clear, that a single polyphenol is impacting several cellular pathways. Thus, a network approach is becoming feasible, describing the interaction of a single polyphenol with cellular networks. Here we have selected icariin to draw a prototypic network of icariin activities. Icariin appears to be a promising drug to treat major age-related diseases, like neurodegeneration, memory and depressive disorders, chronic inflammation, diabetes, and osteoporosis. It interacts with several relevant pathways, like PDE, TGF-ß, MAPK, PPAR, NOS, IGF, Sirtuin, and others. Such networks will be useful to future comparative studies of complex effects of polyphenols.
Asunto(s)
Envejecimiento , Flavonoides/farmacología , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/genética , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/genética , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/metabolismo , Expresión Génica , Humanos , Inflamación/tratamiento farmacológico , Hepatopatías/tratamiento farmacológico , Hepatopatías/genética , Enfermedades Musculares/tratamiento farmacológico , Enfermedades Musculares/genética , Enfermedades Neurodegenerativas/tratamiento farmacológico , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Osteoporosis/tratamiento farmacológico , PPAR alfa/genética , PPAR alfa/metabolismo , Polifenoles/farmacología , Sirtuina 1/genéticaRESUMEN
Nanomaterials are a challenge to toxicology. The high diversity of novel materials and products will require extensive expertize for evaluation and regulatory efforts. Nanomaterials are of substantial scientific and economic potential. Here, we will focus on nanosilver, a material not only with medical applications, but a rapidly increasing use in surprisingly many products. Consequently, toxicological evaluation has to cover an increasing range of complex topics. The toxicology of nanosilver is advancing rapidly; regulatory efforts by Federal Drug Agency and European Environment Protection Agencies are substantial. Current toxicological data, ranging from in vitro studies with cell lines to rodent experiments and ecological evaluation, are numerous, and many groups are providing continuously new data. However, standard classification based on nanosize only is neglecting nanoshape, which adds another level of complexity to the analysis of biological effects. A surprising neglect in nanosilver toxicology so far is the analysis of effects of nanosilver on amyloidosis. Amyloid diseases are widespread in humans and a severe health hazard. The known potential of silver to stimulate amyloidosis in rodents will require a timely and balanced evaluation of nanosilvers.