Application of MAO-A/B subtype activity detection in diagnosis and treatment of neurological diseases / 中国临床药理学与治疗学

The abnormal expression of monoamine oxidases (MAOs), which distributed on the outer mitochondrial membrane can cause the dysfunction of neurotransmitter delivery and related to mental and neurodegenerative diseases. Therefore, the specific detection of MAOs (MAO-A/B) and the regulation of their activities will contribute to the diagnosis and treatment of neurological diseases. In order to distinguish the two subtypes of MAO-A/B, fluorescence detection and imaging techniques with highly specific and sensitive properties have important biological relevance. Herein, our research group based on the concept of "spatial configuration conversion" have designed the two-photon small molecule fluorogenic probes of U1 and F1, which capable of specific fluorescence "Switch-ON" behaviour, and combined with two-photon fluorescence microscopic imaging technology to realize the activity detection of endogenous MAO-B/A in cells and tissues. It is hoped that this works will benefit the understanding of physiological function about MAOs and developing innovative inhibitors, as well as diagnosing and treating in neurological diseases.

Flavoproteínas que actúan como amino-oxidasas: Estructura, función e importancia clínica / Flavoproteins acting as amine oxidases: Structure, function and clinical significance / Flavoproteínas atuando como amina oxidases: Estrutura, função e significado clínico

Se destaca la actividad de las flavoenzimas como amino-oxidasas, que intervienen en el metabolismo de las aminas biogénicas como biorreguladores, especialmente en el crecimiento y la diferenciación celular. La clasificación de las amino-oxidasas incluye flavoenzimas y quinoenzimas. Se analizan las amino-oxidasas que son flavoproteínas, como las monoamino-oxidasas y las poliamino-oxidasas. Se discuten las isoformas, estructuras y función de ambas, sus sustratos e inhibidores, la expresión de MAO-A y MAO-B en tejidos humanos y sus implicancias clínicas. MAO plaquetaria es un biomarcador de desórdenes mentales y neurodegenerativos. Los inhibidores selectivos de MAO-A resultaron ser eficaces antidepresivos, mientras que algunos de MAO-B se utilizan en el tratamiento de enfermedades de Parkinson y de Alzheimer. La identificación de elevadas concentraciones de poliaminas en varias enfermedades, desde cáncer y psoriasis hasta infecciones parasitarias, hace que la manipulación de su metabolismo sea un blanco terapéutico o preventivo en ciertas enfermedades. Se discute además qué poliamino-oxidasas actúan en el metabolismo de las poliaminas en humanos, frente a las presentes en plantas, bacterias y protistas. Las poliaminas y las enzimas de su metabolismo desempeñan funciones relevantes en los procesos de envejecimiento y en algunas enfermedades, como cáncer, diabetes mellitus, accidentes cerebro-vasculares, insuficiencia renal y trastornos psiquiátricos.

The activity of flavoenzymes as amine oxidases involved in the metabolism of biogenic amines as bioregulators is highlighted, particularly for cell growth and differentiation. The classification of amine oxidases includes flavoenzymes and quinoenzymes. Amine oxidases that are flavoproteins, such as monoamine oxidases and polyamine oxidases, are analyzed herein. The isoforms, structures and functions of both enzyme families, their substrates and inhibitors, the expression of MAO-A and MAO-B in human tissues, and their clinical implications are discussed. Platelet MAO is a biomarker of mental and neurodegenerative disorders. Selective MAO-A inhibitors proved to be effective antidepressants, while some MAO-B inhibitors are used for treatment of Parkinson's and Alzheimer's diseases. The identification of high concentrations of polyamines in a variety of diseases, from psoriasis to cancer and parasitic infections, makes handling their metabolism a therapeutic or preventive target for the treatment of some diseases. Also polyamine oxidase activity on polyamine metabolism in humans, compared to those present in plants, bacteria and protists,is discussed. Polyamines and the enzymes involved in their metabolism play important roles in the aging processes, as well as in certain diseases such as cancer, diabetes mellitus, stroke, kidney failure, and defined psychiatric disorders.

Foi enfatizada a atividade de flavoenzimas como as amina oxidases envolvidas no metabolismo de aminas biogênicas como biorreguladores, especialmente no crescimento e diferenciação celular. A classificação das amina oxidases inclui flavoenzimas e quinoenzimas. Amina oxidases que são flavoproteínas, tais como monoamina oxidases e poliamina oxidases, são analisadas. Isoformas, estrutura e função das duas oxidases são discutidas, os seus substratos e inibidores, a expressão de MAO-A e MAO-B em tecidos humanos e suas implicações clínicas. MAO plaquetária é um biomarcador de desordens mentais e neurodegenerativas. Os inibidores selectivos da MAO-A resultaram ser eficazes antidepressivos, embora alguns dos MAO-B sejam utilizados no tratamento da doença de Parkinson e de Alzheimer. A identificação de elevadas concentrações de poliaminas em várias doenças, desde câncer e psoríase a infecções parasitárias, faz com que a manipulação do seu metabolismo seja um alvo terapêutico ou preventivo em certas doenças. Também se discute que a poliamina oxidase atua sobre o metabolismo das poliaminas no ser humano, em comparação com aquelas presentes em plantas, bactérias e protistas. As poliaminas e enzimas do seu metabolismo desempenham papéis relevantes nos processos de envelhecimento e em algumas doenças, tais como câncer, diabetes miellitus, acidente vascular cerebral, insuficiência renal e perturbações psiquiátricas.

Role of H2O2 and cell wall monoamine oxidases in germination of Vigna radiata seeds.

Plant cell wall expresses monoamine oxidases (MAOs) that catalyze oxidation of secreted amines and produce H2O2 in the process. The H2O2, so produced is used by cell wall peroxidases for lignification of cell wall or for plant defense. The natural substrates for these MAOs are elusive, but polyamines and certain catecholamines have been proposed as candidates. Reactive oxygen species are also known to act as signaling molecules controlling plant metabolism. Mungbean (Vigna radiata) has long served as the plant model of choice while studying molecular programs followed during germination and seed development. In this study, we tested the effect of externally added MAO substrates epinephrine and H2O2 on storage protein mobilization in germinating seeds of Vigna radiata. The seeds were imbibed in the presence of 50 M epinephrine and 10 M H2O2. These low concentrations of the two compounds were used to exclude direct effects on proteolysis and were arrived at after testing a range of the two and choosing the most effective concentration. These seeds showed 11% and 7% decrease in fresh weight respectively, indicating greater storage mobilization and a corresponding 19% and 46% increase in axis length as compared to untreated seeds. Soluble protein in seeds treated with epinephrine and H2O2 decreased significantly by 34% and 33% as compared to untreated seeds. Electrophoretic analysis of seed proteins revealed a startling and selective depletion of storage proteins in treated seeds. The results indicated a clear involvement of H2O2 in storage protein mobilization in the cotyledons. We propose that H2O2 generated within cell walls of seeds serves as a signaling molecule guiding germination events, including protein reserve mobilization.