Current review on inducible nitric oxide   synthase and Src tyrosine kinase inhibitors as   disease-modifiers in preclinical models of epilepsy

Thimmasettappa Thippeswamy; Suraj Sundara Vasanthi

Publication:
Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy

dc.contributor.author	Thimmasettappa Thippeswamy
dc.contributor.author	Suraj Sundara Vasanthi
dc.contributor.department	Biología Celular e Histología
dc.contributor.editor	Universidad de Murcia, Departamento de Biologia Celular e Histiologia
dc.date.accessioned	2026-05-13T08:42:45Z
dc.date.available	2026-05-13T08:42:45Z
dc.date.issued	2026
dc.description.abstract	Acute exposure to seizurogenic chemicals, such as organophosphates (OPs) or domoic acid (kainate analogue), can trigger status epilepticus (SE), marked by central (seizures) and, with OPs, peripheral effects due to irreversible inhibition of acetylcholinesterase (AChE). The initial seizurogenic activity in the brain initiates a cascade of molecular and cellular changes, known as epileptogenesis, the process by which epilepsy develops. Among the several signaling pathways involved in epileptogenesis, this review discusses the roles of the Src family of tyrosine kinases (SFK), especially Fyn kinase, and inducible nitric oxide synthase (iNOS) mediated mechanisms. Both signaling molecules are upregulated following initial seizures and persist for a long time, contributing to neuroinflammation, elevated levels of reactive oxygen and nitrogen species (ROS/RNS), and proinflammatory cytokines, as well as neuro degeneration and spontaneously recurring seizures. Epilepsy is a progressive disease associated with unprovoked seizures and cognitive decline. While the current standard of care can alleviate symptoms and reduce mortality, they do not address long-term neurological consequences. In this review, we discuss preclinical testing of two CNS-targeted drugs, iNOS and SFK inhibitors 1400W and Saracatinib (SAR; AZD0530), respectively, as potential disease-modifiers.
dc.format	application/pdf
dc.format.extent	25
dc.identifier.doi	https://doi.org/10.14670/HH-25-022
dc.identifier.eissn	1699-5848
dc.identifier.issn	0213-3911
dc.identifier.uri	http://hdl.handle.net/10201/231701
dc.language	eng
dc.relation	Sin financiación externa a la Universidad
dc.rights	Attribution-NonCommercial-NoDerivatives 4.0 International	*
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject	Acetylcholinesterase
dc.subject	Organophosphate
dc.subject	Src family of tyrosine kinases
dc.subject	Inducible nitric oxide synthase
dc.subject	Status epilepticus
dc.subject.ods	No relacionado con ningún objetivo de desarrollo sostenible
dc.title	Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy
dc.type	info:eu-repo/semantics/article
dspace.entity.type	Publication