Molecular and Cellular Mechanisms of Synaptopathies

Abstract

Synapses, contact points between neurons, are essential elements supporting the ability of neurons to communicate and to transmit relevant information to each other. They play an integral role in brain development and wiring neurons into neural circuits, for example, those related to our behavior. Therefore, alterations affecting the integrity and/or functionality of synapses can lead to synaptic pathologies or synaptopathies. For instance, many neurological disorders including Alzheimer’s disease, Down syndrome, epilepsy, and Parkinson’s disease and neurodevelopmental disorders such as autism spectrum disorders, intellectual disability, and fragile X syndrome have consistently been reported to exhibit abnormalities in synaptic composition, morphology, and function. This special issue discusses various aspects of the molecular interactions that underlie synaptic protein networks and the complex signaling pathways that are activated by them, knowledge that is crucial to understand the cellular and molecular mechanisms involved in different synaptopathies. Synapses comprise a presynaptic compartment, consisting of the axon terminal and their protein machinery implicated in the release of neurotransmitters. Upon exocytosis of presynaptic vesicles, neurotransmitters spill out into the extracellular space called the “synaptic cleft” and diffuse to reach a postsynaptic compartment, composed of the protein machinery that receives and transduces the neurotransmitter-induced signals [1]. Most synaptopathies directly or indirectly affect the molecular repertoire of synaptic proteins.