A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular Level
Increasing evidence links chronic neurodegenerative diseases with neuroinflammation; it is known that neuroprotective agents are capable of modulating the inflammatory processes, that occur with the onset of neurodegeneration pathologies. Here, with the intention of providing a means for active comp...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7175 |
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| author | Marcella Massimini Benedetta Bachetti Elena Dalle Vedove Alessia Benvenga Francesco Di Pierro Nicola Bernabò |
| author_facet | Marcella Massimini Benedetta Bachetti Elena Dalle Vedove Alessia Benvenga Francesco Di Pierro Nicola Bernabò |
| author_sort | Marcella Massimini |
| collection | DOAJ |
| description | Increasing evidence links chronic neurodegenerative diseases with neuroinflammation; it is known that neuroprotective agents are capable of modulating the inflammatory processes, that occur with the onset of neurodegeneration pathologies. Here, with the intention of providing a means for active compounds’ screening, a dysregulation of neuronal inflammatory marker genes was induced and subjected to neuroprotective active principles, with the aim of selecting a set of inflammatory marker genes linked to neurodegenerative diseases. Considering the important role of microglia in neurodegeneration, a murine co-culture of hippocampal cells and inflamed microglia cells was set up. The evaluation of differentially expressed genes and subsequent in silico analysis showed the main dysregulated genes in both cells and the principal inflammatory processes involved in the model. Among the identified genes, a well-defined set was chosen, selecting those in which a role in human neurodegenerative progression in vivo was already defined in literature, matched with the rate of prediction derived from the Principal Component Analysis (PCA) of in vitro treatment-affected genes variation. The obtained panel of dysregulated target genes, including <i>Cxcl9 (Chemokine (C-X-C motif) ligand 9)</i>, <i>C4b (Complement Component 4B)</i>, <i>Stc1 (Stanniocalcin 1)</i>, <i>Abcb1a (ATP Binding Cassette Subfamily B Member 1)</i>, <i>Hp (Haptoglobin)</i> and <i>Adm (Adrenomedullin)</i>, can be considered an in vitro tool to select old and new active compounds directed to neuroinflammation. |
| first_indexed | 2024-03-09T21:49:51Z |
| format | Article |
| id | doaj.art-68be9ce2fd1a4491b69d43984457589f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:49:51Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-68be9ce2fd1a4491b69d43984457589f2023-11-23T20:09:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313717510.3390/ijms23137175A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular LevelMarcella Massimini0Benedetta Bachetti1Elena Dalle Vedove2Alessia Benvenga3Francesco Di Pierro4Nicola Bernabò5Faculty of Veterinary Medicine, University of Teramo, 64100 Teramo, ItalyR&D Division, C.I.A.M. Srl, 63100 Ascoli Piceno, ItalyR&D Division, C.I.A.M. Srl, 63100 Ascoli Piceno, ItalyR&D Division, C.I.A.M. Srl, 63100 Ascoli Piceno, ItalyVelleja Research, 20125 Milan, ItalyFaculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, ItalyIncreasing evidence links chronic neurodegenerative diseases with neuroinflammation; it is known that neuroprotective agents are capable of modulating the inflammatory processes, that occur with the onset of neurodegeneration pathologies. Here, with the intention of providing a means for active compounds’ screening, a dysregulation of neuronal inflammatory marker genes was induced and subjected to neuroprotective active principles, with the aim of selecting a set of inflammatory marker genes linked to neurodegenerative diseases. Considering the important role of microglia in neurodegeneration, a murine co-culture of hippocampal cells and inflamed microglia cells was set up. The evaluation of differentially expressed genes and subsequent in silico analysis showed the main dysregulated genes in both cells and the principal inflammatory processes involved in the model. Among the identified genes, a well-defined set was chosen, selecting those in which a role in human neurodegenerative progression in vivo was already defined in literature, matched with the rate of prediction derived from the Principal Component Analysis (PCA) of in vitro treatment-affected genes variation. The obtained panel of dysregulated target genes, including <i>Cxcl9 (Chemokine (C-X-C motif) ligand 9)</i>, <i>C4b (Complement Component 4B)</i>, <i>Stc1 (Stanniocalcin 1)</i>, <i>Abcb1a (ATP Binding Cassette Subfamily B Member 1)</i>, <i>Hp (Haptoglobin)</i> and <i>Adm (Adrenomedullin)</i>, can be considered an in vitro tool to select old and new active compounds directed to neuroinflammation.https://www.mdpi.com/1422-0067/23/13/7175preclinical screeningin vitro alternative methodsneurodegenerationtranswell co-cultureinflammation |
| spellingShingle | Marcella Massimini Benedetta Bachetti Elena Dalle Vedove Alessia Benvenga Francesco Di Pierro Nicola Bernabò A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular Level International Journal of Molecular Sciences preclinical screening in vitro alternative methods neurodegeneration transwell co-culture inflammation |
| title | A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular Level |
| title_full | A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular Level |
| title_fullStr | A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular Level |
| title_full_unstemmed | A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular Level |
| title_short | A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular Level |
| title_sort | set of dysregulated target genes to reduce neuroinflammation at molecular level |
| topic | preclinical screening in vitro alternative methods neurodegeneration transwell co-culture inflammation |
| url | https://www.mdpi.com/1422-0067/23/13/7175 |
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