PDZ domain-mediated protein interactions: therapeutic targets in neurological disorders

Protein-protein interactions are critical for cellular functioning, and their deregulation is involved in several diseases. Targeting these protein interacting domains could be a promising approach in drug designing. One such domain, the PDZ domain is encoded by several proteins of the nervous system in particular at the postsynaptic density site of neurons where they contribute to signal transduction pathways and neurotransmission. Since PDZ domains have well-defined binding sites, often corresponding to short amino acid motifs at the C-termini of target partner proteins, they provide promising targets for drug discovery. Viruses are art master in manipulating the signaling machinery of the cell they infect. Some of them such as rabies virus which promotes neuron survival by disrupting peculiar PDZ complexes can serve as a source of inspiration for the design of new neuroprotective drugs. This review highlights PDZ-mediated protein interactions in nervous system and their therapeutic potential.