Análise proteômica do secretoma obtido a partir do meio da cultura de células de pacientes com esquizofrenia e controle

A esquizofrenia é uma doença psiquiátrica complexa, sendo influenciada por fatores genéticos e ambientais. Sendo que os sintomas podem ser organizados 3 classes principais de sintomas:positivos, negativos e cognitivos. O principal meio de tratamento da esquizofrenia são as drogas antipsicóticas, utilizadas geralmente na fase aguda da doença para aliviar principalmente os sintomas positivos. O proteoma corresponde ao conjunto de proteínas expressas em um indivíduo em determinadas condições fisiológicas, sendo possível através da análise proteômica identificar proteínas e relacioná-las com a vias metabólicas em que elas atuam. Este estudo analisou o proteoma do secretoma obtido a partir do meio de cultura de células progenitoras neurais de pacientes com esquizofrenia, comparando com o controle. A fim de identificar possíveis proteínas diferentemente expressas, bem como vias metabólicas, que possam estar relacionadas com a fisiopatologia da esquizofreniaFil: Gouvêa-Junqueira, Danielle. Universidade Estadual de Campinas (Brasil).Fil: Martins-de-Souza, Daniel . Universidade Estadual de Campinas (Brasil).Fil: Zuccoli, Giuliana S.. Universidade Estadual de Campinas (Brasil).Fil: Nascimento, Juliana M.. Universidade Estadual de Campinas (Brasil)

The Energy Metabolism Dysfunction in Psychiatric Disorders Postmortem Brains: Focus on Proteomic Evidence

Psychiatric disorders represent a great medical and social challenge and people suffering from these conditions face many impairments regarding personal and professional life. In addition, a mental disorder will manifest itself in approximately one quarter of the world's population at some period of their life. Dysfunction in energy metabolism is one of the most consistent scientific findings associated with these disorders. With this is mind, this review compiled data on disturbances in energy metabolism found by proteomic analyses of postmortem brains collected from patients affected by the most prevalent psychiatric disorders: schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD). We searched in the PubMed database to gather the studies and compiled all the differentially expressed proteins reported in each work. SCZ studies revealed 92 differentially expressed proteins related to energy metabolism, while 95 proteins were discovered in BPD, and 41 proteins in MDD. With the compiled data, it was possible to determine which proteins related to energy metabolism were found to be altered in all the disorders as well as which ones were altered exclusively in one of them. In conclusion, the information gathered in this work could contribute to a better understanding of the impaired metabolic mechanisms and hopefully bring insights into the underlying neuropathology of psychiatric disorders

Protein Succinylation and Malonylation as Potential Biomarkers in Schizophrenia

Two protein post-translational modifications, lysine succinylation and malonylation, are implicated in protein regulation, glycolysis, and energy metabolism. The precursors of these modifications, succinyl-CoA and malonyl-CoA, are key players in central metabolic processes. Both modification profiles have been proven to be responsive to metabolic stimuli, such as hypoxia. As mitochondrial dysfunction and metabolic dysregulation are implicated in schizophrenia and other psychiatric illnesses, these modification profiles have the potential to reveal yet another layer of protein regulation and can furthermore represent targets for biomarkers that are indicative of disease as well as its progression and treatment. In this work, data from shotgun mass spectrometry-based quantitative proteomics were compiled and analyzed to probe the succinylome and malonylome of postmortem brain tissue from patients with schizophrenia against controls and the human oligodendrocyte precursor cell line MO3.13 with the dizocilpine chemical model for schizophrenia, three antipsychotics, and co-treatments. Several changes in the succinylome and malonylome were seen in these comparisons, revealing these modifications to be a largely under-studied yet important form of protein regulation with broad potential applications

Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms

ABSTRACTLong-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target