Investigação de potencias marcadores moleculares no transtorno depressivo resistente através da abordagem in sílico

Abstract

Major depressive disorder is a disease that affects around 320 million people worldwide, and about 50 to 60% of these individuals do not respond to first-line drugs. We still don't have knowledge about the molecular markers involved in the failure in pharmacological response. Thus, this work used in silico analysis in three organisms to assist in this evaluation. A systematic literature review was performed from the articles published in the PubMed database, those articles were screened and manually curated, as well as the selection of proteins and genes related to TRD. Therefore, a protein-protein interaction network could be constructed for each organism, and other protein networks with central action in regions such as prefrontal cortex and hippocampus were derived from these networks. This led to proteins such as AMPA receptor subunit (Gria4), proteins related to neuronal survival and plasticity (BDNF and Mapk1) and proteins related to down-regulated BDNF transcription (AKT1, mTOR and Creb1). And proteins such as NMDA glutamate receptor subunits (Grin1, Grin2, Grin2b and Grin3a), proteins related to cell death and necrosis signaling (Gsk3a, Gsk3b and TNF), tryptophan-to-kynurenine conversion-related protein (Ido1) and pro-inflammatory interleukins (Il1b and Il6) up-regulated. In this way we believe that these proteins may be potential markers of TRD and could be used for preclinical studies as therapeutic targets in high-performance psychiatry. [resumo fornecido pelo autor]