Nerves, heal thyselves

Weizmann Institute scientists reveal key part of nerve regeneration mechanism

A new study conducted by Weizmann Institute scientists has now uncovered a key process leading to the regeneration of peripheral nerves. Nerves in the peripheral nervous system (any part of the body aside from the brain and spinal cord) are capable of regenerating, though often they do so poorly or slowly. Scientists have been trying to understand how they regenerate in order to better treat damage to the peripheral nervous system.
In addition, knowing how these neurons regenerate could provide insights into fixing neurons in the central nervous system where damage is irreversible.

Nerve cells are uniquely shaped, consisting of a cell body from which a long “arm,” called an axon, extends. Axons can reach up to one meter in length and are the main conduit for nerve communication throughout our bodies, by conveying electric signals to muscles or other cells. Due to their great length, axons, like electrical or telecommunications lines, are vulnerable to damage. When a power line goes down in a storm, monitoring systems raise the alarm and repair crews are dispatched to the site. How does an axon ’raise the alarm’ after damage in our own bodies?

In a study published in Neuron, Dr. Michael Fainzilber and Ph.D. students Shlomit Hanz and Eran Pearlson of the Biological Chemistry Department have now shown that a special protein is produced at the site of damage in the axon. Called importin beta, it normally resides far away from the axon, near the nucleus of nerve cells. There, it facilitates the entry of molecules into the nucleus along with its “sister” molecule, importin alpha.

The scientists found that importin beta is produced in the axons upon injury. It then binds to importing alpha, which is normally present in axons, and to proteins that contain the “healing message” (which still have to be identified). The whole group fastens itself to an “engine” called dynein that chugs along “tracks” leading from the axon to the nucleus. The protein complex gains easy entrance to the nucleus due to the presence of importin alpha and beta. The researchers found that blocking this newly uncovered process inhibits nerve regeneration (photos available).

The identification of the proteins containing the “healing message” and of the genes that enable the healing response is the next step in unlocking the mystery of peripheral nerve regeneration.

Since the central and peripheral systems are connected to each other, the ability to transfer substances within the peripheral nervous system could one day offer a springboard from which to introduce therapeutic agents into the brain and spinal cord.

Dr. Michael Fainzilber’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine, the Irwin Green Alzheimer’s Research Fund, the Koshland Research Fund, and the Buddy Taub Foundation. Dr. Fainzilber is the incumbent of the Daniel E. Koshland Sr. Career Development Chair.