Molecular Mechanisms Underlying Neurotransmitter Release: SNARE Proteins, ¿ Synuclein and Movement disorders

Neural signal transmission in the central and peripheral nervous systems relies on a complex and precise event at axonal terminals of neurons, where synaptic vesicles containing neurotransmitter molecules fuse with the presynaptic membrane and release their contents into the synaptic cleft. This rapid and accurate process results from the dynamic coordination of a specialized set of proteins, each playing a vital role in recognition, docking, fusion, and release.Among these molecules, the SNARE protein family-including synaptobrevin (VAMP), syntaxin, and SNAP-25-possesses a sophisticated and specialized structure composed of ¿-helical regions. During membrane fusion, they form a four-helix bundle complex, bringing the two lipid bilayers closer together and facilitating vesicle-neuronal membrane fusion.Synaptotagmin, a calcium-binding protein, contains two C2 domains (C2A and C2B) that selectively bind calcium ions and phospholipids. Acting as a calcium sensor, it responds to sudden increases in intracellular calcium levels and triggers vesicle fusion.Synaptophysin, a four-transmembrane domain protein, is primarily known as a marker of synaptic vesicles.