MicroRNA-based therapy: a new dimension in epilepsy treatment

Abstract

Epilepsy is a brain disorder, which is characterized by a predisposition to generate seizures that are associated with neurobiological, psychological cognitive and linguistic problems. Current treatments of epilepsy remain difficult, and antiepileptic drugs fail for some patients. Expressions of different microRNAs (miRNAs) in different brain regions are implicated in epileptogenic activity. MiRNAs are important regulators of seizure-induced neuronal death. The activation of inflammatory pathways is involved in reactive astrocytes and cells of the microglia in human temporal lobe epilepsy (TLE). MiRNAs are regulators of the innate immune response in the modulation of astrocyte-mediated inflammation. These miRNAs can possibly be used as a novel therapeutic target in the treatment of TLE. Targeting miRNA in epilepsy supports it as a feasible strategy for the treatment of epilepsy. But this powerful technique has received less attention as a potential therapeutic strategy. This is mainly because of the lack of well-defined targets in epilepsy. This review focuses on the role of miRNA in epilepsy, and recent advances in miRNA targeted epileptic therapies.

Angiotensin II and its receptor in activated microglia enhanced neuronal loss and cognitive impairment following pilocarpine-induced status epilepticus

“…However, the mechanism of cognitive impairment is not clear. Studies on epilepsy have shown that cognitive impairment is dependent on the degree of microglial activation and inflammation (Otte et al, 2012;Liu et al, 2013), possibly involving proinflammatory cytokines (e.g. TNF-α and IL-6).…”

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches

“…Micro RNA (MiRs) have also emerged as key players that regulates seizure‐induced neuronal death and the innate immune response in the modulation of astrocyte‐mediated inflammation (Liu et al . ). In an experimental model of autoimmune encephalomyelitis (AE)‐related epilepsy, MiRs‐129‐5p prevents the development of AE‐related epilepsy via targeting HMGB1 expression and inhibiting TLR4/NF‐kB signaling axis.…”

Synthesis of a FTO Inhibitor with Anticonvulsant Activity

“…A BBB-penetrating small molecule inhibitor may provide an advantage over the use of siRNA to modulate FTO. Similarly, this approach may have an advantage over antagomir-based methods to modulate miRNA that have been proposed for the treatment of epilepsy . While we cannot definitively state at this time that the inhibition of FTO is the cause of the anticonvulsant activity and of the modulation of miRNA, there is considerable emerging discussion describing a functional, interdependent role of these activities.…”