Expert Opin Ther Targets. 2025 Oct 4. doi: 10.1080/14728222.2025.2571057. Online ahead of print.
ABSTRACT
INTRODUCTION: Epilepsy often presents numerous comorbidities, including anxiety, depression, and cognitive deficits. Epilepsy is not only restricted to GABA/glutamate imbalance, as researchers are delving more into finding the possible causal inference between other factors; one such recognized interplay is between seizures, stress, and inflammation. Stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation increases corticosteroid release, which binds to mineralocorticoid receptors (MR), intensifies the release of neuroinflammatory markers, lowers seizure threshold, and worsens seizure susceptibility.
AREAS COVERED: Recent studies have demonstrated the potential advantages of MR antagonists in lowering seizure susceptibility. MR antagonists reestablish the equilibrium between MRs and GRs by inhibiting corticosteroid binding on MRs, thereby maintaining the balance between pro- and anti-inflammatory mediators. MR antagonists have been undergoing clinical trials as adjuvant therapy for management of psychological disorders by reducing neuroinflammation and altering body’s reaction to stress. In addition to assessing the possible contribution of MR antagonists in the reduction of comorbidities linked to epilepsy, this review also elucidates mechanisms that underlie the connection between seizures, stress, and inflammation.
EXPERT OPINION: By addressing these gaps, future research can provide a more comprehensive understanding of MR signaling in epilepsy, ultimately leading to personalized treatment strategies and novel therapeutic targets.
PMID:41046158 | DOI:10.1080/14728222.2025.2571057
Recent Comments