Bilateral crosstalk of rho- and extracellular-signal-regulated-kinase (ERK) pathways is confined to an unidirectional mode in spinal muscular atrophy (SMA) |
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| Affiliation: | 1. Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany;2. Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany;3. Niedersachsen Research Network on Neuroinfection (N-RENNT), Germany;1. Department of Neurology, “G. Jazzolino” Hospital, Vibo Valentia, Italy;2. Department of Neurology, Sant''Anna Hospital, Como, Italy;3. Stroke Unit, Mondino IRCCS, Pavia, Italy;4. Department of Interventional Radiology, University of Florence, Florence, Italy;5. Department of Neurology, “G. da Saliceto” Hospital, Piacenza, Italy;6. Department of Emergency Neurology, Mondino IRCCS, Pavia, Italy;7. Stroke Unit, Sant''Andrea Hospital, Sapienza University, Rome, Italy;8. Department of Neurology, Niguarda Ca’ Granda Hospital, Milan, Italy;9. Neurology and Psychiatry Department, Sapienza University, Rome, Italy;10. NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy |
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| Abstract: | Rho-kinase (ROCK) as well as extracellular signal regulated kinase (ERK) control actin cytoskeletal organization thereby regulating dynamic changes of cellular morphology. In neurons, motility processes such as axonal guidance and neurite outgrowth demand a fine regulation of upstream pathways. Here we demonstrate a bilateral ROCK–ERK information flow in neurons. This process is shifted towards an unidirectional crosstalk in a model of the neurodegenerative disease Spinal Muscular Atrophy (SMA), ultimately leading to neurite outgrowth dysregulations. As both pathways are of therapeutic relevance for SMA, our results argue for a combinatorial ROCK/ERK-targeting as a future treatment strategy. |
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