The Potential Role of Polyamines in Epilepsy and Epilepsy-Related Pathophysiological Changes

Abstract

Epilepsy is one of the most common neurological disorders and severely impacts the life quality of patients. Polyamines are ubiquitous, positively charged aliphatic amines that are present at a relatively high level and help regulate the maintenance of cell membrane excitability and neuronal physiological functions in the central nervous system. Studies have shown abnormalities in the synthesis and catabolism of polyamines in patients with epilepsy and in animal models of epilepsy. The polyamine system seems to involve in the pathophysiological processes of epilepsy via several mechanisms such as the regulation of ion permeability via interaction with ion channels, involvement in antioxidation as hydroperoxide scavengers, and the induction of cell damage via the production of toxic metabolites. In this review, we try to describe the possible associations between polyamines and epilepsy and speculate that the polyamine system is a potential target for the development of novel strategies for epilepsy treatment.

Keywords: epilepsy; neuroprotection; neurotoxicity; pathological change; polyamine metabolism; seizure.

Figure 1

Cationic forms and structures of the three major polyamines in mammalian cells under physiological pH.

Figure 2

Biosynthesis and metabolism of polyamines.

Figure 3

The key role of H₂O₂ in the positive cell-death-signal-generating cycle via the action of SAT1 and PAOX. Adapted with permission from ref. [38]. Copyright 2003 Wallace, H.M.

Figure 4

The main role of polyamines in different ion channels and receptors.

Figure 5

Pathological changes progress and vary with epileptogenesis and the development of epilepsy. Adapted with permission from ref. [146]. Copyright 2019 Elsevier.

Figure 6

Apoptotic pathways that alteration of endogenous polyamine levels may involve. Adapted from ref. [239].