Abstract
Epilepsy is one of the most common serious brain diseases worldwide. Programmed cell death (PCD), a cellular self-destruction phenomenon, has been greatly documented in neurodegenerative diseases. Pyroptosis is a well-known pro-inflammatory PCD, and its involvement in epilepsy has been reported in animal models of epilepsy and also epileptic patients. Canonical (caspase-1-dependent) and non-canonical (caspase-1-independent) pathways are two main mechanisms implicated in pyroptotic cell death. Mouse caspase-11 or human analogues caspase-4/5 induce the non-canonical pathway. In both pathways, membrane gasdermin (GSDMD) pores contribute to pro-inflammatory cytokine release and lead to membrane destabilization and cell lysis. IL-1β and IL-18 are pro-inflammatory cytokines that are released following pyroptotic PCD. Brain inflammation increases excitability in the nervous system, promotes seizure activity, and is probably associated with the molecular and synaptic changes involved in epileptogenesis. Pro-inflammatory cytokines affect the glutamate and GABA neurotransmitter release as well as their receptors, thereby resulting in seizure activity. This review is intended to provide an overview of the current published works on pyroptotic cell death in epilepsy. The mechanisms by which pro-inflammatory cytokines, including IL-1β and IL-18 can promote epileptic discharges were also collected. According to this survey, since the involvement of pyroptosis in the development of epilepsy has been established, pyroptosis-targeted therapies may represent a novel anti-epileptogenic strategy.
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PMM contributed to the study conception and design. The first draft of the manuscript was written by HKA (the introduction part), and PMM (all of the other parts). RA commented on previous versions of the manuscript. He provided valuable scientific and linguistic editing of the manuscript. NE contributed to the designing of the figure. All authors read and approved the final manuscript.
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Atabaki, R., Khaleghzadeh-Ahangar, H., Esmaeili, N. et al. Role of Pyroptosis, a Pro-inflammatory Programmed Cell Death, in Epilepsy. Cell Mol Neurobiol 43, 1049–1059 (2023). https://doi.org/10.1007/s10571-022-01250-3
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DOI: https://doi.org/10.1007/s10571-022-01250-3