Mechanisms of Synaptic Plasticity Disruption in Epilepsy: Advances in Understanding and Therapeutic Innovations

This review study provides an in-depth examination of the processes underlying synaptic plasticity disruption in epilepsy, with a focus on recent advances in understanding and treatment development. Epilepsy is a common neurological disorder affecting around 1% of the global population. It is characterised by recurrent, unprovoked seizures caused by aberrant brain activity. The condition impacts various aspects of life, including cognitive function and emotional well-being. Recent research has shown synaptic plasticity — the capacity of synapses to develop or weaken over time — as an important role in epilepsy aetiology. Aberrant synaptic plasticity, such as excessive long-term potentiation (LTP) and deficient long-term depression (LTD), contributes to the formation of hyperexcitable brain circuits and increases seizure risk. In epilepsy, key mechanisms impacting synaptic plasticity include neurotransmitter imbalances, synaptic remodelling, inflammatory responses, and genetic and epigenetic factors. Despite the availability of antiepileptic medications (AEDs), approximately one-third of patients remain resistant to treatment, emphasising the need for innovative therapeutic methods. Current treatment approaches include AEDs, surgical procedures, metabolic therapies, and new treatments such as gene therapy and nanotechnology-based solutions. The aim of this critical review is to comprehend and target maladaptive alterations in synaptic plasticity with the intent to develop more effective therapies. It explores innovative treatment targets, precision medicine, advanced neuromodulation techniques, and the integration of epigenetic therapies. This research addresses not only future goals but also the challenges hindering the development of novel treatments, given the complexity of synaptic plasticity and the heterogeneity of epilepsy. This will be critical for overcoming present therapy barriers and improving patient outcomes.