Fungal Protein Stimulates Axon Regeneration Via 14-3-3 Protein-Protein Stabilization; Work Identifies Possible Targets of Future Drug Development for Spinal Cord Injury & Stroke

A foray into plant biology has led one researcher to discover that a natural molecule can stimulate the repair of axons, the thread-like projections that carry electrical signals between neurons. Axonal damage is the major culprit underlying disability in conditions such as spinal cord injury and stroke. Andrew Kaplan, a Ph.D. candidate at the Montreal Neurological Institute and Hospital of McGill University in Canada, was looking for a pharmacological approach to axon regeneration, with a focus on 14-3-3, a family of proteins with neuroprotective functions that have been under investigation in the laboratory of Dr. Alyson Fournier, Professor of Neurology and Neurosurgery and senior author on the study. During Kaplan’s search, he found research describing how plants respond to a specific type of fungal infection. When plants are exposed to fusicoccin-A, a small molecule produced by a certain strain of fungus, the leaves of the plant wilt, but the roots grow longer. Fusicoccin-A affects 14-3-3 activity by stabilizing its interactions with other proteins. "While 14-3-3 is the common denominator in this phenomenon, the identity of the other proteins involved and the resulting biological activities differ between plants and animals," says Kaplan. He theorized that fusicoccin-A could be an effective way of harnessing 14-3-3 to repair axons. To test this theory, he and his fellow researchers treated mechanically damaged neurons in culture with the molecule and observed the results. "When I looked under the microscope the following day, the axons were growing like weeds, an exciting result that led us to determine that fusicoccin-A can stimulate axon repair in the injured nervous system," says Kaplan. The new work was published online on March 8, 2017 in Neuron.
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