Impairment of the neurotrophic signaling hub B-Raf contributes to motoneuron degeneration in spinal muscular atrophy
Niko Hensel, Federica Cieri, Pamela Santonicola, Ines Tapken, Tobias Schüning, Michela Taiana, Elisa Pagliari, Antonia Joseph, Silke Fischer, Natascha Heidrich, Hella Brinkmann, Sabrina Kubinski, Anke K. Bergmann, Manuela Richter, Klaus Jung, Stefania Corti, Elia Di Schiavi, Peter Claus
Abstract
Significance The mechanisms of neurodegeneration are important targets for future treatments of the devastating motoneuron disease spinal muscular atrophy (SMA). Here, we show an altered signaling network in SMA models and patient cells with a reduced B-Raf expression in the network center. B-Raf is crucial for motoneuron survival, and we present data that B-Raf restoration ameliorates motoneuron loss and symptoms in SMA models.
Topics & Concepts
SMA*Spinal muscular atrophySMN1BiologyNeuroscienceMotor neuronSignal transductionNeurotrophic factorsMAPK/ERK pathwayNeurodegenerationSpinal cordCell biologyMedicineGeneticsGeneDiseaseInternal medicineReceptorMathematicsCombinatoricsNeurogenetic and Muscular Disorders ResearchRNA modifications and cancerRNA Research and Splicing