Hemozoin induces malaria via activation of DNA damage, p38 MAPK and neurodegenerative pathways in a human iPSC-derived neuronal model of cerebral malaria.
Cerebral malaria
DNA damage
Hemozoin
Neuro-inflammation
Neurons
iPSCs
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 10 2024
23 10 2024
Historique:
received:
13
03
2024
accepted:
11
10
2024
medline:
23
10
2024
pubmed:
23
10
2024
entrez:
22
10
2024
Statut:
epublish
Résumé
Malaria caused by Plasmodium falciparum infection results in severe complications including cerebral malaria (CM), in which approximately 30% of patients end up with neurological sequelae. Sparse in vitro cell culture-based experimental models which recapitulate the molecular basis of CM in humans has impeded progress in our understanding of its etiology. This study employed healthy human induced pluripotent stem cells (iPSCs)-derived neuronal cultures stimulated with hemozoin (HMZ) - the malarial toxin as a model for CM. Secretome, qRT-PCR, Metascape, and KEGG pathway analyses were conducted to assess elevated proteins, genes, and pathways. Neuronal cultures treated with HMZ showed enhanced secretion of interferon-gamma (IFN-γ), interleukin (IL)1-beta (IL-1β), IL-8 and IL-16. Enrichment analysis revealed malaria, positive regulation of cytokine production and positive regulation of mitogen-activated protein kinase (MAPK) cascade which confirm inflammatory response to HMZ exposure. KEGG assessment revealed up-regulation of malaria, MAPK and neurodegenerative diseases-associated pathways which corroborates findings from previous studies. Additionally, HMZ induced DNA damage in neurons. This study has unveiled that exposure of neuronal cultures to HMZ, activates molecules and pathways similar to those observed in CM and neurodegenerative diseases. Furthermore, our model is an alternative to rodent experimental models of CM.
Identifiants
pubmed: 39438620
doi: 10.1038/s41598-024-76259-3
pii: 10.1038/s41598-024-76259-3
doi:
Substances chimiques
hemozoin
39404-00-7
Hemeproteins
0
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24959Informations de copyright
© 2024. The Author(s).
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