Grant: Operating Grant

Peripheral nerves are the essential connections that exist between the brain and spinal cord, and the body. Without peripheral nerves, there is no movement, no sensation. Damage and disease of peripheral nerves (neuropathy is a disease of the peripheral nerve) are very common, usually irreversible and disabling. Out lab is interested in a new approach toward improving regeneration of peripheral nerves. This approach involves inhibiting molecular "brakes" or roadblocks that exist within nerve cells and that restrain growth. While restraint may be necessary in normal stable adults, these roadblocks limit regenerative growth of neurons. Two molecules, named PTEN and RHOA are key roadblocks and our laboratory has evidence that by inhibiting either, improved regeneration activity ensues. We propose to evaluate mechanisms of their action, the long term impact on regrowth of nerves when they are inhibited and whether these molecules operate together or are independent "brakes". If independent, inhibiting both may have substantial benefits during regeneration after nerve injury or neuropathy. Our work focuses on neurons in culture, nerve regeneration in rats and mice and occurs within a milieu of several neuroscientists interested in improving the outcome of regeneration.