Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

Martins-de-Souza, Daniel; Gattaz, Wagner F.; Schmitt, Andrea; Novello, José Camillo; Marangoni, Sérgio; Turck, Christoph W.; Dias-Neto, Emmanuel

doi:10.1186/1471-244x-9-17

Cited by 128 publications

(81 citation statements)

References 56 publications

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“…Although it is expected that altered expression of Prdx6 might be seen with conditions that are clearly associated with oxidant stress, proteomic screens have frequently demonstrated that altered Prdx6 expression occurs in diseases where the involvement of oxidant stress is less clear. High expression of Prdx6 has been noted in degenerative afflictions of the central nervous system, including Alzheimer's (77), Parkinson's (79), Pick's (42), and CrutzfeldJakob diseases (43), schizophrenia (57), and an experimental mouse model of amyotrophic lateral sclerosis (91). As a potential mechanism for some of these associations, binding of Prdx6 to the protein saitohin may be linked to tau splicing and subsequent neurodegeneration (26).…”

Section: Prdx6 In the Pathobiology Of Diseasementioning

confidence: 99%

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Fisher

2011

Antioxidants & Redox Signaling

337

327

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Peroxiredoxin 6 (Prdx6) is the prototype and the only mammalian 1-Cys member of the Prdx family. Major differences from 2-Cys Prdxs include the use of glutathione (GSH) instead of thioredoxin as the physiological reductant, heterodimerization with pGSH S-transferase as part of the catalytic cycle, and the ability either to reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or to hydrolyze the sn-2 ester (alkyl) bond of phospholipids (phospholipase A 2 [PLA 2 ] activity). The bifunctional protein has separate active sites for peroxidase (C47, R132, H39) and PLA 2 (S32, D140, H26) activities. These activities are dependent on binding of the protein to phospholipids at acidic pH and to oxidized phospholipids at cytosolic pH. Prdx6 can be phosphorylated by MAP kinases at T177, which markedly increases its PLA 2 activity and broadens its pH-activity spectrum. Prdx6 is primarily cytosolic but also is targeted to acidic organelles (lysosomes, lamellar bodies) by a specific targeting sequence (amino acids 31-40). Oxidant stress and keratinocyte growth factor are potent regulators of Prdx6 gene expression. Prdx6 has important roles in both antioxidant defense based on its ability to reduce peroxidized membrane phospholipids and in phospholipid homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipid synthesis. Antioxid. Redox Signal. 15, 831-844.

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Section: Prdx6 In the Pathobiology Of Diseasementioning

confidence: 99%

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Fisher

2011

Antioxidants & Redox Signaling

337

327

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“…These proteins might also be potential biomarkers for schizophrenia 65 . The oligodendrocyte protein ermin was found to be upregulated in the prefrontal cortex and downregulated in the temporal cortex in two used shotgun proteomic studies 66,67 . Brockschnieder et al 68 concluded that ermin probably contributes to the maintenance and stabilization of the myelin sheath in the adult brain.…”

Section: Disturbed Macroconnectivity: Evidence From Cellular and Molementioning

confidence: 99%

“…In nerve terminals, crystalline mu modulates cytoskeletal proteins 89 . In a proteomic study, this cytoskeletal protein has been reported to be upregulated in the prefrontal cortex in schizophrenia 66 . Increased expression of crystalline mu in schizophrenia has also been reported in transcriptome studies 53,90 .…”

Section: Schizophrenia As a Disorder Of Disturbed Synaptic Plasticitymentioning

confidence: 99%

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

Schmitt

Reich‐Erkelenz²,

Gebicke‐Härter

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Schizophrenia is a severe neurobiological disease with genetic and environmental factors playing a role in the pathophysiology. Several brain regions have been implicated in the disease process and are connected in complex neuronal circuits. On the cellular and molecular level, affected connectivity between these regions, involving dysfunctional myelination of neuronal axons, as well as alterations on the synaptic level and energy metabolism of neurons leading to disturbances in synaptic plasticity are major findings in post-mortem studies. Microarray studies investigating genome-wide gene expression have contributed to the findings of alterations in complex pathways in relevant brain regions in schizophrenia. Moreover, first laser-capture microdissection studies allowed the investigation of gene expression in specific groups of neurons. However, it must be kept in mind that in post-mortem studies confounding effects of medication, mRNA quality as well as the capability of the brain for neuroplastic regenerative mechanisms in individuals with a lifetime history of schizophrenia may influence the complex pattern of alterations on the molecular level. Despite these limitations, hypothesis-free transcriptome studies in brain tissue from schizophrenia patients offer a unique possibility to learn more about underlying mechanisms, leading to new insights in the pathophysiology of the disease. A, et al. / Rev Psiq Clín. 2013;40(1):10-5 Keywords: Schizophrenia, gene expression, microarray, RT-PCR, in situ hybridization, brain regions. Schmitt ResumoEsquizofrenia é uma severa doença neurobiológica com fatores genéticos e ambientais desempenhando um papel na fisiopatologia. Diversas regiões cerebrais têm sido implicadas no processo da doença e estão conectadas em complexos circuitos neuronais. Nos níveis molecular e celular, a conectividade afetada entre essas regiões, envolvendo mielinização disfuncional dos axônios neuronais, bem como as alterações no nível sináptico e metabolismo energético levando a distúrbios na plasticidade sináptica, são os maiores achados em estudos post-mortem. Estudos de microarranjos investigando a expressão gênica contribuíram para os achados de alterações em vias complexas em regiões cerebrais relevantes na esquizofrenia. Além disso, estudos utilizando microdissecção e captura a laser permitiram a investigação da expressão gênica em grupos específicos de neurônios. Entretanto, deve ser mantido em mente que em estudos post-mortem, confusos efeitos de medicação, qualidade de RNAm, bem como capacidade de mecanismos regenerativos neuroplásticos do cérebro em indivíduos com história de vida de esquizofrenia, podem influenciar o complexo padrão de alterações no nível molecular. Apesar dessas limitações, estudos transcriptômicos livres de hipóteses em tecido cerebral de pacientes esquizofrênicos oferecem uma possibilidade única para aprender mais sobre os mecanismos subjacentes, levando a novas ópticas da fisiopatologia da doença. A, et al. / Rev Psiq Clín. 2013;40(1):10-5 Palavras-cha...

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“…The genetic proile of mitochondria and energy metabolism in the analysis of brain samples may contribute to reveal the novel insight to the etiology of schizophrenia [73,74]. The genetic interactions and intermediate mediators among mitochondrial genes and many underexpressed SCZCGs indicate the genetic predisposition of mitochondria dysfunction in schizophrenia.…”

Section: Mitochondrial Dysfunction In Schizophrenia By Genetic Interamentioning

confidence: 99%

Transcriptome Analysis of Systems Biology for Schizophrenia

Huang¹,

Tsao²,

Wang³

et al. 2016

Schizophrenia Treatment - The New Facets

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Transcriptome analysis of postmortem brain samples provides more insights to evaluate biological dysfunctions by analysis of diferential expression and genetic interactions in schizophrenia. The growing development of new technologies such as next-generation sequencing (NGS) helps to explore detailed and underlying molecular changes from global perspective of view, not only focus in single SNP variants. It is implicated that schizophrenia genetic and protein interactions may give rise to biological dysfunction not only in dopamine dysfunction but also in immune, energy metabolism, mitochondrial dysfunction and hemostasis. Epigenetic investigation of schizophrenia provides important information on how the environmental factors afect the genetic architecture of the disease. DNA methylation plays a pivotal role in etiology for schizophrenia. The schizophrenia diferential methylation genes and diferential expression genes were analyzed to ind the potential protein complexes related to the etiology of schizophrenia from alteration of DNA methylation. The protein complexes and pathways involved in schizophrenia diferential methylation network may be responsible for the etiology and potential treatment targets. It is implicated that the interaction between diferential expression candidate genes and diferential methylation genes may describe the global view of disease mechanisms and it has important roles in the pathogenesis for schizophrenia.

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Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

Cited by 128 publications

References 56 publications

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

Transcriptome Analysis of Systems Biology for Schizophrenia

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Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

Cited by 128 publications

References 56 publications

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A2Activities

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A2Activities

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

Transcriptome Analysis of Systems Biology for Schizophrenia

Contact Info

Product

Resources

About

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities