Interactive neuroinflammation pathways and transcriptomics-based identification of drugs and chemical compounds for schizophrenia
- PMID: 37961844
- DOI: 10.1080/15622975.2023.2281514
Interactive neuroinflammation pathways and transcriptomics-based identification of drugs and chemical compounds for schizophrenia
Abstract
Objectives: Schizophrenia is a psychiatric disorder affecting 1% of the population. Accumulating evidence indicates that neuroinflammation is involved in the pathology of these disorders by altering neurodevelopmental processes and specifically affecting glutamatergic signalling and astrocytic functioning. The aim of this study was to curate interactive biological pathways involved in schizophrenia for the identification of novel pharmacological _targets implementing pathway, gene ontology, and network analysis.
Methods: Neuroinflammatory pathways were created using PathVisio and published in WikiPathways. A transcriptomics dataset, originally created by Narla et al. was selected for data visualisation and analysis. Transcriptomics data was visualised within pathways and networks, extended with transcription factors, pathways, and drugs. Network hubs were determined based on degrees of connectivity.
Results: Glutamatergic, immune, and astrocytic signalling as well as extracellular matrix reorganisation were altered in schizophrenia while we did not find an effect on the complement system. Pharmacological agents that _target the glutamate receptor subunits, inflammatory mediators, and metabolic enzymes were identified.
Conclusions: New neuroinflammatory pathways incorporating the extracellular matrix, glutamatergic neurons, and astrocytes in the aetiology of schizophrenia were established. Transcriptomics based network analysis provided novel _targets, including extra-synaptic glutamate receptors, glutamate transporters and extracellular matrix molecules that can be evaluated for therapeutic strategies.
Keywords: Neuroinflammation; metabolic signalling; molecular pathways; network analysis; pathway models; schizophrenia.
Similar articles
-
Allosteric modulators for the treatment of schizophrenia: _targeting glutamatergic networks.Curr Top Med Chem. 2013;13(1):26-54. doi: 10.2174/1568026611313010005. Curr Top Med Chem. 2013. PMID: 23409764 Free PMC article. Review.
-
Neuronal and Astrocytic Regulations in Schizophrenia: A Computational Modelling Study.Front Cell Neurosci. 2021 Aug 26;15:718459. doi: 10.3389/fncel.2021.718459. eCollection 2021. Front Cell Neurosci. 2021. PMID: 34512269 Free PMC article.
-
A network biology workflow to study transcriptomics data of the diabetic liver.BMC Genomics. 2014 Nov 15;15(1):971. doi: 10.1186/1471-2164-15-971. BMC Genomics. 2014. PMID: 25399255 Free PMC article.
-
[Evidence on the key role of the metabotrobic glutamatergic receptors in the pathogenesis of schizophrenia: a "breakthrough" in pharmacological treatment].Riv Psichiatr. 2012 Mar-Apr;47(2):149-69. doi: 10.1708/1069.11719. Riv Psichiatr. 2012. PMID: 22622251 Review. Italian.
-
COVID-19 patient transcriptomic and genomic profiling reveals comorbidity interactions with psychiatric disorders.Transl Psychiatry. 2021 Mar 15;11(1):160. doi: 10.1038/s41398-020-01151-3. Transl Psychiatry. 2021. PMID: 33723208 Free PMC article.
Cited by
-
Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?Brain Sci. 2023 Dec 23;14(1):19. doi: 10.3390/brainsci14010019. Brain Sci. 2023. PMID: 38248234 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical