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

Giulia Spoto; Giulia Valentini; Maria Concetta Saia; Ambra Butera; Greta Amore; Vincenzo Salpietro; Antonio Gennaro Nicotera; Gabriella Di Rosa

doi:10.3389/fneur.2022.826211

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

Front Neurol. 2022 Mar 8:13:826211. doi: 10.3389/fneur.2022.826211. eCollection 2022.

Authors

Giulia Spoto¹, Giulia Valentini¹, Maria Concetta Saia¹, Ambra Butera¹, Greta Amore¹, Vincenzo Salpietro^{2

3

4}, Antonio Gennaro Nicotera¹, Gabriella Di Rosa¹

Affiliations

¹ Unit of Child Neurology and Psychiatry, Department of Human Pathology of the Adult and Developmental Age "Gaetano Barresi", University of Messina, Messina, Italy.
² Department of Neuromuscular Disorders, Institute of Neurology, University College London, London, United Kingdom.
³ Pediatric Neurology and Muscular Diseases Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Giannina Gaslini, Genoa, Italy.
⁴ Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.

Abstract

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.

Keywords: SNAREopathies; developmental and epileptic encephalopathy (DEE); drug resistant epilepsy; intellectual disability (ID); pre-synaptic mechanisms; synaptopathy.

Publication types

Review