Role of astrocyte senescence regulated by the non- canonical autophagy in the neuroinflammation associated to cerebral malaria. - Université de Lille Accéder directement au contenu
Article Dans Une Revue Brain, behavior, and immunity Année : 2024

Role of astrocyte senescence regulated by the non- canonical autophagy in the neuroinflammation associated to cerebral malaria.

Résumé

Background Cerebral malaria (CM) is a fatal neuroinflammatory syndrome caused (in humans) by the protozoa Plasmodium (P.) falciparum. Glial cell activation is one of the mechanisms that contributes to neuroinflammation in CM. Result By studying a mouse model of CM (caused by P. berghei ANKA), we describe that the induction of autophagy promoted p21-dependent senescence in astrocytes and that CXCL-10 was part of the senescence-associated secretory phenotype. Furthermore, p21 expression was observed in post-mortem brain and peripheral blood samples from patients with CM. Lastly, we found that the depletion of senescent astrocytes with senolytic drugs abrogated inflammation and protected mice from CM. Conclusion Our data provide evidence for a novel mechanism through which astrocytes could be involved in the neuropathophysiology of CM. p21 gene expression in blood cell and an elevated plasma CXCL-10 concentration could be valuable biomarkers of CM in humans. In the end, we believe senolytic drugs shall open up new avenues to develop newer treatment options.
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hal-04489105 , version 1 (04-03-2024)

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Fatima Hellani, Inès Leleu, Nasreddine Saidi, Nathalie Martin, Cecile Lecoeur, et al.. Role of astrocyte senescence regulated by the non- canonical autophagy in the neuroinflammation associated to cerebral malaria.. Brain, behavior, and immunity, 2024, Brain, Behavior, and Immunity, 117, p. 20-35. ⟨10.1016/j.bbi.2023.12.030⟩. ⟨hal-04489105⟩
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