Fatty Acid Binding Proteins (FABP7s) Anandamide Carrier Proteins as Potential Medications for Chemotherapy-Induced Neuropathies

Abstract

The endocannabinoids anandamide (arachidonoylethanolamine, AEA) and 2-arachidonoyl glycerol (2AG) are neuromodulatory lipids involved in cell signaling that affects pain sensitization, food intake, and reward mechanisms in the brain. Recently, it was reported that fatty acid binding proteins (FABPs), particularly brain FABP (FABP7) and epidermal FABP (FABP5) both of which expressed in brain, can significantly potentiate AEA uptake. The focal drive of this project is to discover selective FABP inhibitors as a potentially new therapeutic modality for treating pain, substance abuse/drug addiction, and other disorders. Towards this goal, we have first expressed recombinant human-brain FABP (FABP7) in Escherichia coli as inclusion bodies. The purified protein was refolded and then characterized by mass spectrometry and multidimensional nuclear magnetic resonance (NMR) spectroscopy. We have also developed a high throughput radioassay protocol for ligand screening and have shown that AEA binds to FABP7 with an affinity of ~1