Speaker
Description
Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects 2.8 million people worldwide. While several treatments are approved to manage the symptoms of MS, there is no cure and there are no treatments that address the root cause of the disease. The symptoms are caused by the degradation of myelin in the central nervous system (CNS), leaving portions of axons damaged and uninsulated. In healthy patients, oligodendrocytes, the myelinating cells of the CNS, would normally travel to sites of myelin damage and repair these demyelinating lesions. However, in MS patients, oligodendrocytes do not undergo healthy development and therefore do not always appreciably repair the myelin damage. A specific lipid and enzyme pair, lysophosphatidic acid (LPA) and autotaxin, has been established to play a key role in oligodendrocyte development, but the signaling pathway of LPA has not been fully characterized. Through our research, we show that inhibiting autotaxin with orthosteric small molecule inhibitors impedes oligodendrocyte development and that this effect can be rescued by the addition of exogenous LPA. We further plan to investigate the lipid profiles of oligodendrocytes at various stages of development to identify signaling lipids that potentially impact oligodendrocyte maturation. Lastly, we are working to synthesize a bifunctional LPA probe to identify novel binding partners of LPA. By elucidating the mechanisms of LPA action, we could develop better therapeutic strategies to target this pathway and treat MS.
| Talk Credit? | No |
|---|
