Session 2, Abstract 7
GREEN TEA POLYPHENOLS INDUCE INTERNALIZATION OF NOGO-A RECEPTOR AND DESENSITIZE NEURONS TO AXONAL GROWTH INHIBITOR NOGO-A
Sarah Zhou* (Rayudu Gopalakrishna), University of Southern California, Dept. of Cell and Neurobiology, 1333 San Pablo Street, Los Angeles, CA 90033.
The limited treatment options for stroke and its few possibilities of recovery make it a major cause of disability. To be effective, post-stroke therapies would regenerate axons from remaining neurons. However, after CNS injury, myelin-derived inhibitors such as Nogo-A prevent axonal regeneration. The development of synthetic drugs for stroke recovery is a daunting task. Therefore, the use of natural products such as green tea polyphenols (GTPP), which are safe, may complement ongoing efforts in the development of therapies. Epigallocatechin-3-gallate (EGCG) is the active ingredient of GTPP. We tested a GTPP mixture and pure EGCG on nerve growth factor-differentiated Neuroscreen-1 cells and mouse primary cortical neurons and found that both treatments prevent Nogo-A’s ability to inhibit neurite outgrowth as well as to cause growth cone collapse. Our results suggest that EGCG, by binding to the cell-surface 67-kD laminin receptor (67LR), induced intracellular elevation of cAMP. Furthermore, we found that cAMP caused internalization of Nogo-A receptor (NgR1). This prevented Nogo-A’s ability to inhibit neurite outgrowth and to cause growth cone collapse. As there currently is a dearth of stroke recovery treatments, understanding the mechanisms of natural neuroregenerative agents such as green tea polyphenols could provide opportunities to develop new therapies for stroke recovery.