Speaker
Description
Multiple sclerosis (MS) is a common neurodegenerative disease that has limited treatment options and involves the demyelination of axons within the central nervous system. Myelin sheaths are formed by oligodendrocytes, and this process is regulated by various lipid signaling molecules. One known signaling lipid is lysophosphatidic acid (LPA), which is made from the enzymatic action of autotaxin on lysophosphatidylcholine (LPC). However, previous studies have not fully defined the mechanism by which LPA production promotes myelination. Fluorescence resonance energy transfer (FRET) LPC probes will be developed to monitor autotaxin activity and LPA production in real time during oligodendrocyte differentiation. Two probes will be synthesized, a fluorescence-on and a fluorescence-off probe, which will allow for tracking of autotaxin activity and location within cells. Once these probes have been characterized by 1H nuclear magnetic spectroscopy and mass spectroscopy, they will be evaluated for their performance in vitro to determine which probe provides enhanced fluorescent imaging ability and enzyme activity. The identified probe will then be applied to primary cultures of rodent oligodendrocyte precursor cells (OPCs) and two-photon microscopy will be used to image the probe and autotaxin activity within cells. These studies will provide further insight into the location and activity of LPA production and its involvement in OPC differentiation and myelination, which may reveal new possible targets for future treatment of neurological diseases involving myelination.
