Synaptotagmin V Inhibitors

Synaptotagmin V (SytV) is a synaptic vesicle protein that plays a crucial role in neurotransmitter release at neuronal synapses. It is primarily involved in calcium-dependent exocytosis, where it acts as a calcium sensor to trigger vesicle fusion with the plasma membrane, leading to neurotransmitter release into the synaptic cleft. SytV contains tandem C2 domains that bind calcium ions, allowing it to undergo conformational changes upon calcium binding, thereby facilitating membrane fusion. Additionally, SytV has been implicated in regulating synaptic vesicle trafficking and recycling, further highlighting its significance in neurotransmission.

Inhibition of Synaptotagmin V can occur through various mechanisms aimed at disrupting its calcium-sensing and membrane fusion functions. One potential strategy involves targeting the calcium-binding sites within its C2 domains, thereby preventing its conformational changes and subsequent vesicle fusion. Additionally, interference with the protein-protein interactions essential for SytV's recruitment to the synaptic vesicle membrane or its interaction with other synaptic proteins could hinder its function. Another approach may involve modulating downstream signaling pathways associated with SytV-mediated neurotransmitter release, such as protein kinases or phosphatases that regulate synaptic vesicle exocytosis.