Can a systems approach produce a better understanding of mood disorders?

Background: One in twenty-five people suffer from a mood disorder. Current treatments are sub-optimal with poor patient response and uncertain modes-of-action. There is thus a need to better understand underlying mechanisms that determine mood, and how these go wrong in affective disorders. Systems biology approaches have yielded important biological discoveries for other complex diseases such as cancer, and their potential in affective disorders will be reviewed. Scope of review: This review will provide a general background to affective disorders, plus an outline of experimental and computational systems biology. The current application of these approaches in understanding affective disorders will be considered, and future recommendations made. Major conclusions: Experimental systems biology has been applied to the study of affective disorders, especially at the genome and transcriptomic levels. However, data generation has been slowed by a lack of human tissue or suitable animal models. At present, computational systems biology has only be applied to understanding affective disorders on a few occasions. These studies provide sufficient novel biological insight to motivate further use of computational biology in this field. General significance: In common with many complex diseases much time and money has been spent on the generation of large-scale experimental datasets. The next step is to use the emerging computational approaches, predominantly developed in the field of oncology, to leverage the most biological insight from these datasets. This will lead to the critical breakthroughs required for more effective diagnosis, stratification and treatment of affective disorders

ANHIDRASA CARBÓNICA DE Plasmodium falciparum: UN BLANCO ÚTIL PARA EL DISEÑO DE MEDICAMENTOS ANTIMALÁRICOS Y COMPUESTOS BLOQUEADORES DE LA TRANSMISIÓN DE MALARIA CARBONIC ANHYDRASE IN Plasmodium falciparum: A USEFUL TARGET FOR ANTIMALARIAL DRUG DESIGNING AND MALARIA BLOCKING TRANSMISSION COMPOUNDS

La anhidrasa carbónica es una metaloenzima que cataliza la conversión reversible del CO2 a bicarbonato, un componente metabólico indispensable para la síntesis de pirimidinas de novo por Plasmodium spp y los procesos de exflagelación llevados a cabo por el parásito al interior del mosquito vector. La enzima participa además en el transporte del bicarbonato dentro y fuera de las células para evitar un desequilibrio en el sistema CO2/HCO3- y la alteración del pH al interior de las células y en el espacio intercelular. Por lo tanto, al inhibir la enzima, ya sea en el parásito o en el insecto vector, se podría conducir a una disminución de la replicación y al detrimento y/o muerte del parásito. De esta forma, los inhibidores de anhidrasa carbónica constituyen una alternativa, tanto terapéutica como de bloqueo de la transmisión, para el control de la malaria. La actividad anti-Plasmodium in vitro de algunos compuestos inhibidores de anhidrasa carbónica ya se ha determinado. Sin embargo, la eficacia in vivo y el mecanismo por el cual los inhibidores son capaces de afectar el desarrollo del parásito en los mosquitos vectores permanecen aún por evaluarse. En el marco del proyecto de investigación "Evaluación de inhibidores de anhidrasa carbónica como medidas terapéuticas y de bloqueo de la transmisión de malaria" este artículo presenta una revisión del estado del arte sobre el papel de la anhidrasa carbónica de Plasmodium spp y el uso de inhibidores específicos de esta enzima como una estrategia para el tratamiento de la malaria y el bloqueo de la transmisión de la enfermedad. Se incluyeron artículos publicados en los últimos 59 años, identificados a partir de la bases de datos bibliográficos PubMed y ScienceDirect, cruzando las palabras claves, al igual que artículos recopilados por los autores y se analizan e integran los resultados de investigaciones publicadas alrededor del tema.Carbonic anhydrase is a metalloenzyme that catalyzes the reversible conversion of CO2 to bicarbonate, an essential metabolic component used by the malaria parasites for de novo synthesis of pyrimidines and the exflagelation of gametocytes inside the mosquito vector. Carbonic anhydrase is involved in the transport of bicarbonate. This enzyme participates in transport of bicarbonate inside and outside the cells to avoid an imbalance in the system CO2/HCO3- and alteration of pH in the interior of the cell as well as in the intercellular space. Therefore, inhibition of this enzyme either in the parasite or the insect vector, could lead to a decrease in replication and to the detriment and/or death of the parasite. Given the importance of carbonic anhydrase in the metabolism, development and survival of Plasmodium, it could be postulated that carbonic anhydrase inhibitors are both a therapeutic and a blocking transmission alternative. Previous studies have demonstrated the in vitro anti-Plasmodium activity of some inhibitors. However, it is necessary to determine their effectiveness to confirm its usefulness in the treatment or blocking malaria transmission and the mechanism by which these inhibitors are able to affect the development of the parasite in the mosquito vector. In this paper we present a review about the role of carbonic anhydrase in Plasmodium spp and using some specific inhibitors as a strategy for malaria treatment and transmission blocking strategy. Articles published in the past 59 years identified from bibliographic database (PubMed and ScienceDirect) and papers collected by the authors were included

New model of action for mood stabilizers: phosphoproteome from rat pre-frontal cortex synaptoneurosomal preparations.

BACKGROUND: Mitochondrial short and long-range movements are necessary to generate the energy needed for synaptic signaling and plasticity. Therefore, an effective mechanism to transport and anchor mitochondria to pre- and post-synaptic terminals is as important as functional mitochondria in neuronal firing. Mitochondrial movement range is regulated by phosphorylation of cytoskeletal and motor proteins in addition to changes in mitochondrial membrane potential. Movement direction is regulated by serotonin and dopamine levels. However, data on mitochondrial movement defects and their involvement in defective signaling and neuroplasticity in relationship with mood disorders is scarce. We have previously reported the effects of lithium, valproate and a new antipsychotic, paliperidone on protein expression levels at the synaptic level. HYPOTHESIS: Mitochondrial function defects have recently been implicated in schizophrenia and bipolar disorder. We postulate that mood stabilizer treatment has a profound effect on mitochondrial function, synaptic plasticity, mitochondrial migration and direction of movement. METHODS: Synaptoneurosomal preparations from rat pre-frontal cortex were obtained after 28 daily intraperitoneal injections of lithium, valproate and paliperidone. Phosphorylated proteins were identified using 2D-DIGE and nano LC-ESI tandem mass spectrometry. RESULTS: Lithium, valproate and paliperidone had a substantial and common effect on the phosphorylation state of specific actin, tubulin and myosin isoforms as well as other proteins associated with neurofilaments. Furthermore, different subunits from complex III and V of the electron transfer chain were heavily phosphorylated by treatment with these drugs indicating selective phosphorylation. CONCLUSIONS: Mood stabilizers have an effect on mitochondrial function, mitochondrial movement and the direction of this movement. The implications of these findings will contribute to novel insights regarding clinical treatment and the mode of action of these drugs