Synaptopathies in Developmental and Epileptic Encephalopathies: A Focus on Pre-synaptic Dysfunction

The proper connection between the pre- and post-synaptic nervous cells depends on any element constituting the synapse: the pre- and post-synaptic membranes, the synaptic cleft, and the surrounding glial cells and extracellular matrix. An alteration of the mechanisms regulating the physiological synergy among these synaptic components is defined as synaptopathy. Mutations in the genes encoding for proteins involved in neuronal transmission are associated with several neuropsychiatric disorders, but only some of them are associated with Developmental and Epileptic Encephalopathies (DEEs). These conditions include a heterogeneous group of epilepsy syndromes associated with cognitive disturbances/intellectual disability, autistic features, and movement disorders. This review aims to elucidate the pathogenesis of these conditions, focusing on mechanisms affecting the neuronal pre-synaptic terminal and its role in the onset of DEEs, including potential therapeutic approaches.

Automated summary

The proper connection between pre- and post-synaptic nervous cells relies on various components including membranes, the synaptic cleft, glial cells, and extracellular matrix. Synaptopathy refers to the alteration of mechanisms regulating these synaptic components and is associated with neuropsychiatric disorders. Developmental and Epileptic Encephalopathies (DEEs) are a group of epilepsy syndromes associated with cognitive disturbances, intellectual disability, autistic features, and movement disorders. This review focuses on the pathogenesis of DEEs, particularly on the role of pre-synaptic terminals and potential therapeutic approaches.