SYT1-Associated Neurodevelopmental Disorder: A Narrative Review

Abstract

Synaptic dysregulations often result in damaging effects on the central nervous system, resulting in a wide range of brain and neurodevelopment disorders that are caused by mutations disrupting synaptic proteins. SYT1, an identified synaptotagmin protein, plays an essential role in mediating the release of calcium-triggered neurotransmitters (NT) involved in regular synaptic vesicle exocytosis. Considering the significant role of SYT1 in the physiology of synaptic neurotransmission, dysfunction and degeneration of this protein can result in a severe neurological impairment. Genetic variants lead to a newly discovered rare disorder, known as SYT1-associated neurodevelopment disorder. In this review, we will discuss in depth the function of SYT1 in synapse and the underlying molecular mechanisms. We will highlight the genetic basis of SYT1-associated neurodevelopmental disorder along with known phenotypes, with possible interventions and direction of research.

Keywords: genetic disorder; intellectual disability; neurodevelopment; neurotransmission; synapse; synaptic vesicles; synaptotagmin.

Figure 1

Synaptotagmin-1 Function in Neurotransmission. SYT1 plays a pivotal role in synaptic neurotransmission as a dual Ca²⁺sensor able to carry out both endocytosis and exocytosis independently. This figure describes the release of neurotransmitters following the detection of high concentrations of Ca²⁺ by SYT1’s C2B domains.