By: Seth Palmer
A protein called spastin, which plays a critical role in axon regeneration, is encoded in humans by a dominant disease gene known as SPG4.
When a single copy of the SPG4 gene is disrupted, axons are unable to regenerate, and affected individuals develop a disorder known as hereditary spastic paraplegia (HSP), characterized by progressive lower-limb weakness and spasticity as long-motor axons in the spinal cord degenerate.
Interestingly, an impaired spastin (SPG4) gene does not appear to affect axons' development — only their regeneration after injury — and dendrites, nerve-cell components that receive information from other cells and the outside world, continue to function normally and regenerate after injury.
"Now that we know that spastin plays an important role in axon regeneration and also that this gene is dominant, we have opened up a possible path toward the study of human diseases involving nerve-cell impairment," says Dr. Rolls. "We are hopeful that this discovery will open the door to new research related to spinal-cord and other neurological disorders in humans."
For lead author Michelle Stone, this project's impetus is highly personal — as Dr. Rolls and Ms. Stone explain:
“Michelle was really the driving force behind our lab’s interest in neuronal responses to injury and stress," says Dr. Rolls. "She has developed simple and powerful assays in Drosophila that are allowing us to start to dissect molecular mechanisms that promote positive outcomes from neuronal injury.”
Ms. Stone adds, "My father had a massive stroke in his early fifties which was quite devastating for our family. Although he made significant progress in his recovery, to this day he still lives with the challenges of limited sight, speech and mobility. With the support of my mentor, Dr. Rolls, I have been able to investigate how neurons respond to injuries such as stroke, and it is my hope that our work will contribute to the understanding of mechanisms to increase neuronal recovery after injury."
About the researchers
cell and developmental biology, genetics, and neuroscience, a researcher in the Center for Molecular Investigation of Neurological Disorders, and is the director of the Center for Cellular Dynamics.is an assistant professor of biochemistry and molecular biology, a co-funded faculty member of the Huck Institutes' graduate programs in
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