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 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 Cxcl9 (Chemokine (C-X-C motif) ligand 9), C4b (Complement Component 4B), Stc1 (Stanniocalcin 1), Abcb1a (ATP Binding Cassette Subfamily B Member 1), Hp (Haptoglobin) and Adm (Adrenomedullin), can be considered an in vitro tool to select old and new active compounds directed to neuroinflammation.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

International journal of molecular sciences - 23(2022), 13 vom: 28. Juni

Sprache:

Englisch

Beteiligte Personen:

Massimini, Marcella [VerfasserIn]
Bachetti, Benedetta [VerfasserIn]
Dalle Vedove, Elena [VerfasserIn]
Benvenga, Alessia [VerfasserIn]
Di Pierro, Francesco [VerfasserIn]
Bernabò, Nicola [VerfasserIn]

Links:

Volltext

Themen:

In vitro alternative methods
Inflammation
Journal Article
Neurodegeneration
Neuroprotective Agents
Preclinical screening
Transwell co-culture

Anmerkungen:

Date Completed 12.07.2022

Date Revised 28.03.2023

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms23137175

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM343266687