Publication: Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy
Authors
Thimmasettappa Thippeswamy ; Suraj Sundara Vasanthi
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-25-022
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info:eu-repo/semantics/article
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.
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