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TROY: A Newly Identified Stop Signal in the Pathway for Nerve Regeneration

For release: Wednesday, March 9, 2005

One of the major puzzles in neuroscience is how to get nerves in the brain and spinal cord to regrow after injury.  A new study has identified a protein, TROY, that inhibits nerve cell repair and plays a role in preventing nerve regeneration.  This finding is an important step in developing new methods for treatment of spinal cord injury, stroke, and degenerative nerve disorders such as multiple sclerosis (MS).

Most of the cells in the human body have the ability to repair themselves after injury.  However, neurons in the central nervous system (CNS) are unable to regenerate their injured axons.  One of the major obstacles to regeneration in the adult CNS is the presence of inhibitory molecules that are associated with myelin, a fatty coating that forms a sheath around nerve cells.  Research in recent years has focused on identifying the chain of events that prevents regeneration.  

Part of the inhibitory or “braking” machinery that stops nerve regeneration is Nogo, a protein normally found in myelin.   Studies have suggested that a necessary partner or co-receptor to Nogo is a protein called p75, which is common in the developing nervous system but decreases during adulthood.  However, while most neurons in the central nervous system do not have p75, these neurons still demonstrate myelin inhibition and can not repair themselves. In the new study, Dr. Zhigang He and colleagues from The Children’s Hospital of Harvard Medical School in Boston asked, “Why do neurons without p75 still fail to regenerate after injury?”  Their findings appear in the February 3, 2005, issue of Neuron. This research was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS). 

“We hypothesized that either these neurons without p75 have a completely different mechanism to prevent regeneration, or that a different version of the protein exists,” says Dr. He. “This investigation led us to the newly identified TROY protein, a member of the same receptor family as p75.  While TROY has a similar action to the p75 protein, it is widely expressed throughout the CNS.  TROY also has a well researched biochemical pathway that could help us to possibly target new strategies for clinical therapy.”

This study is the first to show that TROY is a critical player in blocking nerve regeneration.  Although the research does not eliminate the possibility that other molecules are also involved in regeneration, the study helps scientists to understand how myelin inhibition may be regulated.  The finding that more than one protein may be involved in myelin inhibition adds a new level of complexity to designing therapeutic strategies for treating CNS injury.

“Designing a therapeutic strategy to block myelin inhibition would be an efficient way to promote regeneration.  This research may provide important insights into development of future treatment for spinal cord injuries,” says Dr. He.

Researchers caution that any strategy to alter the inhibitor proteins would need to be carefully designed.  Since both p75 and TROY are expressed in many types of cells in the CNS and are also involved in inflammatory responses, simply blocking these proteins could lead to many undesirable side effects.

The discovery of the TROY protein enhances understanding of nerve injury and provides a piece in the puzzle of CNS nerve regeneration.  Investigators hope this information will point to ways to stimulate nerve repair in the brain, which is vital for restoring functions in persons with MS, spinal cord injury, stroke and other CNS injury conditions. 

The NINDS is a component of the National Institutes of Health within the Department of Health and Human Services and is the nation’s primary supporter of biomedical research on the brain and nervous system.

Reference:  Park JB, Yiu G, Kaneko S, Wang J, Chang J, He Z.  “A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors.” Neuron, February 3, 2005, Vol.45, pp.345-351.

--By Michelle D. Jones-London, Ph.D.

Last Modified January 31, 2007