Grant: Project Grant

Damage to nerves in limbs often results in motor and sensory problems because the fibers (axons) that form the nerves do not regrow in large numbers back to their targets. Some of the ensuing problems that occur, such as motor incoordination and neuropathic pain, disrupt the quality of life for millions of humans worldwide and create significant personal and economic burden. More concerning is that regeneration of damaged peripheral nerves declines with age. This deficit has become a pressing clinical issue with the growing maturing population and humans living longer because older individuals experience more peripheral injuries because of muscle weakness and slower reflexes. Since surgical interventions are limited in their efficacy, new and specific therapies are urgently needed. Schwann cells are the glial cells of the peripheral nervous system. They wrap axons with myelin, a fatty substance that acts like an insulator that allows electrical signals to pass rapidly from one nerve cell to another. After peripheral nerve damage, Schwann cells play a critical role in creating a favourable environment for damaged fibers to regrow. They accomplish this by secreting growth factors, remyelinating regrowing axons and removing inhibitory molecules. However, the functions of Schwann cells decline with age and this contributes to the impaired regeneration and thus poor functional recovery seen in older individuals. My lab is interested in understanding why regeneration of damaged peripheral nerves and functional recovery are worse with age. We will specifically investigate whether a protein called alphaB-crystallin (alphaBC) that is expressed by Schwann cells, and whose expression in peripheral nerves reduces as an animal ages, is responsible for the deficit in Schwann cell function and thus poorer regeneration in older injured animals. This grant will also inform us whether alphaBC is a possible therapeutic agent for improving functional recovery in older animals.