Epileptic Phenotypes Associated With SNAREs and Related Synaptic Vesicle Exocytosis Machinery

Abstract

SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptor) are an heterogeneous family of proteins that, together with their key regulators, are implicated in synaptic vesicle exocytosis and synaptic transmission. SNAREs represent the core component of this protein complex. Although the specific mechanisms of the SNARE machinery is still not completely uncovered, studies in recent years have provided a clearer understanding of the interactions regulating the essential fusion machinery for neurotransmitter release. Mutations in genes encoding SNARE proteins or SNARE complex associated proteins have been associated with a variable spectrum of neurological conditions that have been recently defined as “SNAREopathies.” These include neurodevelopmental disorder, autism spectrum disorder (ASD), movement disorders, seizures and epileptiform abnormalities. The SNARE phenotypic spectrum associated with seizures ranges from simple febrile seizures and infantile spasms, to severe early-onset epileptic encephalopathies. Our study aims to review and delineate the epileptic phenotypes associated with dysregulation of synaptic vesicle exocytosis and transmission, focusing on the main proteins of the SNARE core complex (STX1B, VAMP2, SNAP25), tethering complex (STXBP1), and related downstream regulators.

Mendelian Randomization Study Using Dopaminergic Neuron‐Specific eQTL Nominates Potential Causal Genes for Parkinson's Disease

“…STX1B encodes a presynaptic plasma membrane protein that belongs to the syntaxins family. STX1B is a core member of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNAREs), a complex with important roles in synaptic vesicle exocytosis and synaptic transmission 18 . SH3GL2 encodes endophilin A1, a presynaptic protein mediating synaptic vesicle formation 19 .…”

“…STX1B is a core member of the soluble N-ethylmaleimidesensitive factor attachment protein receptor (SNAREs), a complex with important roles in synaptic vesicle exocytosis and synaptic transmission. 18 SH3GL2 encodes endophilin A1, a presynaptic protein mediating synaptic vesicle formation. 19 Interestingly, SH3GL2 could be phosphorylated by LRRK2, a protein encoded by the wellcharacterized PD risk gene LRRK2.…”

Recent Developments in Autism Genetic Research: A Scientometric Review from 2018 to 2022

“…The naming of this cluster is based on a series of two papers written by Hakami [ 208 , 209 ] on antiseizure drugs, and may be related to ASD due to the higher prevalence of seizure and epilepsy diagnoses among these individuals [ 210 ]. Similarly, other contributing papers focused on understanding the genetic bases of epilepsy [ 211 , 212 , 213 ] and epilepsy treatment [ 214 , 215 ]. In this cluster, contributing papers frequently cited references from the International League Against Epilepsy (ILAE) in their clinical descriptions and classifications of different seizures and epilepsies (e.g., Scheffer et al [ 216 ], Fisher et al [ 217 , 218 ] with citation frequencies of 43, 12, and 8, respectively).…”

Clocking Epilepsies: A Chronomodulated Strategy-Based Therapy for Rhythmic Seizures

“…Mutations in the GTPase and the middle domains of DNM1 result in impaired endocytosis of synaptic vesicles, leading to severe seizures with intellectual disability and hypotonia [ 97 ]. STX1B (syntaxin 1b) and STXBP1 (syntaxin-binding protein 1) play a role in exocytosis; specifically, STX1B mainly mediates releasing the Ca 2+ -dependent synaptic vesicle, whereas STXBP1 secures the correct position of syntaxin-1 [ 98 ]. STX1B mutations result in tonic–clonic seizures, absence seizures, and myoclonic seizures [ 99 ].…”

“…STX1B mutations result in tonic–clonic seizures, absence seizures, and myoclonic seizures [ 99 ]. STX1B and STXBP1 mutations are often found in infant seizures [ 98 ].…”