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Proteomics as a tool for understanding schizophrenia.

Martins-de-Souza D - Clin Psychopharmacol Neurosci (2011)

Bottom Line: In the post-genomic era, proteomics has emerged as a promising strategy for revealing disease and treatment biomarkers as well as a tool for the comprehension of the mechanisms of schizophrenia pathobiology.Proteins involved in energy metabolism, calcium homeostasis, myelinization, and cytoskeleton have been recurrently found to be differentially expressed in schizophrenia brains.These findings may encourage new studies on the understanding of schizophrenia biochemical pathways and even new potential drug targets.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute of Psychiatry, Munich, Germany and Lab. de Neurociências (LIM-27), Inst. Psiquiatria, Fac. de Medicina da Universidade de São Paulo, São Paulo, Brazil.

ABSTRACT
Schizophrenia is likely to be a multifactorial disorder, consequence of alterations in gene and protein expression since the neurodevelopment that together to environmental factors will trigger the establishment of the disease. In the post-genomic era, proteomics has emerged as a promising strategy for revealing disease and treatment biomarkers as well as a tool for the comprehension of the mechanisms of schizophrenia pathobiology. Here, there is a discussion of the potential pathways and structures that are compromised in schizophrenia according to proteomic findings while studying five distinct brain regions of post-mortem tissue from schizophrenia patients and controls. Proteins involved in energy metabolism, calcium homeostasis, myelinization, and cytoskeleton have been recurrently found to be differentially expressed in schizophrenia brains. These findings may encourage new studies on the understanding of schizophrenia biochemical pathways and even new potential drug targets.

No MeSH data available.


Related in: MedlinePlus

Glucose metabolic pathway. The black boxes show the differentially expressed enzymes and metabolites revealed by proteomics in the glycolysis found in SCZ brain tissue (Illustration by KEGG - http://www.genome.jp/kegg).37) HK, hexokinase; ALDOC, fructose-bisphosphate aldolase C; TPI1, triosephosphate isomerase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PGK1, phosphoglycerate kinase 1; PGAM1, phosphoglycerate mutase 1; ENO2, gamma-enolase; PKM1, pyruvate kinase isozymes M1/M2; DLD, dihydrolipoyl dehydrogenase, mitochondrial.
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Figure 1: Glucose metabolic pathway. The black boxes show the differentially expressed enzymes and metabolites revealed by proteomics in the glycolysis found in SCZ brain tissue (Illustration by KEGG - http://www.genome.jp/kegg).37) HK, hexokinase; ALDOC, fructose-bisphosphate aldolase C; TPI1, triosephosphate isomerase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PGK1, phosphoglycerate kinase 1; PGAM1, phosphoglycerate mutase 1; ENO2, gamma-enolase; PKM1, pyruvate kinase isozymes M1/M2; DLD, dihydrolipoyl dehydrogenase, mitochondrial.

Mentions: Several enzymes of the glycolysis such as such as hexokinase, triose phosphate isomerase, glyceraldehyde phosphate dehydrogenase, phosphoglyceromutase, enolase, and pyruvate kinase - were found to be differentially expressed in the proteome analyses of SCZ brain tissue. Using a metabolic map as designed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis37) (http://www.genome.jp/kegg) (Fig. 1), we can have a clear look of the influence of glycolysis in SCZ. Compromising glucose metabolism will lead to pivotal alterations in the cellular energy generation. In a tentative of functionally validate the proteomics findings, we quantify relatively the amounts of pyruvate in SCZ compared to controls. In the thalamus of SCZ patients, levels of pyruvate were significantly decreased.24) These findings may lead to therapeutic and pharmacologic targets. Lower levels of pyruvate in SCZ brains may compromise Krebs cycle function, as also supported by our proteomics studies considering the differential expression of aconitase 2 and malate dehydrogenase 1. Moreover, higher levels of nicotinamide adenine dinucleotide phosphate (NADPH) have also been found in the thalamus of SCZ patients,24) which can compromise oxidative phosphorylation (OXPHOS). This is also supported by proteomics since components of the mitochondrial complex I and V are altered in SCZ brains.18) The overall dysregulation of energy metabolism leads to the increased production of hazardous ROS which can trigger oxidative stress events. This processed was also pointed out by proteomics through the differential expression of peroxiredoxins. Moreover, other proteins indicating oxidative stress such as members of gluthatione transferases family, carbonyl reductase (CBR) 1, CBR3 and quinoid dihydropteridine reductase (QDPR) we found to be differentially expressed. The differential expression of transketolase indicates a dysfunction in the pentose phosphate pathway which main function NADPH for OXPHOS. The different levels of NADPH in thalamus interestingly support this finding.24)


Proteomics as a tool for understanding schizophrenia.

Martins-de-Souza D - Clin Psychopharmacol Neurosci (2011)

Glucose metabolic pathway. The black boxes show the differentially expressed enzymes and metabolites revealed by proteomics in the glycolysis found in SCZ brain tissue (Illustration by KEGG - http://www.genome.jp/kegg).37) HK, hexokinase; ALDOC, fructose-bisphosphate aldolase C; TPI1, triosephosphate isomerase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PGK1, phosphoglycerate kinase 1; PGAM1, phosphoglycerate mutase 1; ENO2, gamma-enolase; PKM1, pyruvate kinase isozymes M1/M2; DLD, dihydrolipoyl dehydrogenase, mitochondrial.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569116&req=5

Figure 1: Glucose metabolic pathway. The black boxes show the differentially expressed enzymes and metabolites revealed by proteomics in the glycolysis found in SCZ brain tissue (Illustration by KEGG - http://www.genome.jp/kegg).37) HK, hexokinase; ALDOC, fructose-bisphosphate aldolase C; TPI1, triosephosphate isomerase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PGK1, phosphoglycerate kinase 1; PGAM1, phosphoglycerate mutase 1; ENO2, gamma-enolase; PKM1, pyruvate kinase isozymes M1/M2; DLD, dihydrolipoyl dehydrogenase, mitochondrial.
Mentions: Several enzymes of the glycolysis such as such as hexokinase, triose phosphate isomerase, glyceraldehyde phosphate dehydrogenase, phosphoglyceromutase, enolase, and pyruvate kinase - were found to be differentially expressed in the proteome analyses of SCZ brain tissue. Using a metabolic map as designed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis37) (http://www.genome.jp/kegg) (Fig. 1), we can have a clear look of the influence of glycolysis in SCZ. Compromising glucose metabolism will lead to pivotal alterations in the cellular energy generation. In a tentative of functionally validate the proteomics findings, we quantify relatively the amounts of pyruvate in SCZ compared to controls. In the thalamus of SCZ patients, levels of pyruvate were significantly decreased.24) These findings may lead to therapeutic and pharmacologic targets. Lower levels of pyruvate in SCZ brains may compromise Krebs cycle function, as also supported by our proteomics studies considering the differential expression of aconitase 2 and malate dehydrogenase 1. Moreover, higher levels of nicotinamide adenine dinucleotide phosphate (NADPH) have also been found in the thalamus of SCZ patients,24) which can compromise oxidative phosphorylation (OXPHOS). This is also supported by proteomics since components of the mitochondrial complex I and V are altered in SCZ brains.18) The overall dysregulation of energy metabolism leads to the increased production of hazardous ROS which can trigger oxidative stress events. This processed was also pointed out by proteomics through the differential expression of peroxiredoxins. Moreover, other proteins indicating oxidative stress such as members of gluthatione transferases family, carbonyl reductase (CBR) 1, CBR3 and quinoid dihydropteridine reductase (QDPR) we found to be differentially expressed. The differential expression of transketolase indicates a dysfunction in the pentose phosphate pathway which main function NADPH for OXPHOS. The different levels of NADPH in thalamus interestingly support this finding.24)

Bottom Line: In the post-genomic era, proteomics has emerged as a promising strategy for revealing disease and treatment biomarkers as well as a tool for the comprehension of the mechanisms of schizophrenia pathobiology.Proteins involved in energy metabolism, calcium homeostasis, myelinization, and cytoskeleton have been recurrently found to be differentially expressed in schizophrenia brains.These findings may encourage new studies on the understanding of schizophrenia biochemical pathways and even new potential drug targets.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute of Psychiatry, Munich, Germany and Lab. de Neurociências (LIM-27), Inst. Psiquiatria, Fac. de Medicina da Universidade de São Paulo, São Paulo, Brazil.

ABSTRACT
Schizophrenia is likely to be a multifactorial disorder, consequence of alterations in gene and protein expression since the neurodevelopment that together to environmental factors will trigger the establishment of the disease. In the post-genomic era, proteomics has emerged as a promising strategy for revealing disease and treatment biomarkers as well as a tool for the comprehension of the mechanisms of schizophrenia pathobiology. Here, there is a discussion of the potential pathways and structures that are compromised in schizophrenia according to proteomic findings while studying five distinct brain regions of post-mortem tissue from schizophrenia patients and controls. Proteins involved in energy metabolism, calcium homeostasis, myelinization, and cytoskeleton have been recurrently found to be differentially expressed in schizophrenia brains. These findings may encourage new studies on the understanding of schizophrenia biochemical pathways and even new potential drug targets.

No MeSH data available.


Related in: MedlinePlus