Kevin Park, Ph.D. Assistant Professor, Department of Neurological Surgery / The Miami Project, recently published a manuscript in Cell Reports titled Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co-induce Axon Regrowth in Adult Central Nervous System. In this study, Dr. Park and colleagues examined how a classical transcription factor, known as STAT3 locates to different cellular regions and promotes axon regeneration in the inured central nervous system (CNS). Overall, their data provided mechanistic insights into the mode of actions of STAT3 in mature CNS, and demonstrate that capitalizing STAT3’s effects in combination with modulation of other growth regulating molecules allows a neural intervention for extensive axon regrowth.
“Promoting injured axons to regenerate long distances remains a major challenge, but if effectively attained, could help restore motor and sensory functions that are lost after traumatic injury or in neurodegenerative conditions,” said Dr. Park. “Colleagues and I are further examining the neural regeneration events and assessing whether the regenerated nerve fibers are navigating properly and forming functional connections.”
STAT3 is a transcription factor central to axon regrowth. It has a mysterious ability to act in different subcellular regions independently of its transcriptional roles. However, whether such a mechanism exists in mature central nervous system (CNS) neurons remained questionable. This study demonstrates that along with nuclear translocation, STAT3 translocates to mitochondria in mature CNS neurons upon cytokine stimulation. Loss- and gain-of-function studies using knockout mice and viral expression of various STAT3 mutants demonstrate that STAT3’s transcriptional function is indispensable for CNS axon regrowth whereas mitochondrial STAT3 enhances bioenergetics and further potentiates regrowth.