Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

Author Maes, Michael Google Scholar
Nowak, Gabriel Google Scholar
Caso, Javier R. Google Scholar
Carlos Leza, Juan Google Scholar
Song, Cai Google Scholar
Kubera, Marta Google Scholar
Klein, Hans Google Scholar
Galecki, Piotr Google Scholar
Noto, Cristiano Autor UNIFESP Google Scholar
Glaab, Enrico Google Scholar
Balling, Rudi Google Scholar
Berk, Michael Google Scholar
Abstract Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.
Keywords Depression
Immune
Inflammation
Neuroprogression
Oxidative and nitrosative stress
Leaky gut
IDO
TRYCATs
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor NHMRC: GNT1059660
Grant number NHMRC: GNT1059660
Date 2016
Published in Molecular Neurobiology. New York, v. 53, n. 5, p. 2927-2935, 2016.
ISSN 0893-7648 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 2927-2935
Origin http://dx.doi.org/10.1007/s12035-015-9183-5
Access rights Closed access
Type Article
Web of Science ID WOS:000377935400019
URI https://repositorio.unifesp.br/handle/11600/57694

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