Neuronal transporters

The second major topic of the group is focused on transporters. Presynaptic neurotransmitter vesicles play a key role in the neurotransmitter cycle by stocking and releasing it upon action potential. Vesicular neurotransmitter transporters (VNTs) allow the loading of these vesicles and are thus major actors of the neurotransmission. Initially the project aimed at providing new pharmacological tools, markers and mechanistic insights of the vesicular glutamate transporters (VGLUT). It was then extended to two other members of the same sub-family SLC17, sialin the sialic acid transporter which potentially transports Glu and Asp (Miyaji, 2008) and VNUT the nucleotide transporter characterized in 2008. (Sawada, 2008).

Several sialic acid analogues have been synthesized and tested. We chose the virtual high throughput screening (vHTS) approach to discover new inhibitors of sialin. A homology model was built, validated and docked with per-O-Ac 9-iodo-Neu5Ac a competitive inhibitor. A vHTS provided several hits among which, one was published (FR139317), others are being further evaluated.

Several new neuronal transporters are being investigated.