Spinal Muscular Atrophy (SMA) is a fatal neurodegenerative disease caused by mutations in the Survival of Motoneuron 1 gene (SMN1) that results in low SMN protein levels and consequent loss of motor neurons, the cells that control skeletal muscles and movements.
SMA patients suffer from muscle weakness and atrophy often resulting in respiratory insufficiency and early death. Recently, approved therapies based on SMN restoration dramatically changed the disease natural history. Although the human disease and its murine model counterparts clearly show that SMN deficiency leads to a rather specific motoneuron degeneration, the mechanisms by which this neuronal degeneration occurs in SMA are still largely unknown. A deeper understanding of molecular impairment downstream of SMN-reduction is therefore inherently relevant and may be crucial for the development of new therapeutic approaches.
In a recent study Prof. Stefania Corti, head of Neural Stem Cells Lab of Department of Pathophysiology and Transplantation, “Centro Dino Ferrari” University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico in collaboration whit Prof. Peter Claus of Center for Systems Neurosciences of Hannover Medical School and Dr. Elia Di Schiavi of CNR in Naples, identify an alteration in signaling network linked to a reduction of B-Raf protein in SMA models. They observed that B-Raf was crucial for motor neuron survival and that B-Raf restoration ameliorated motor neuron loss and symptoms in SMA.
These results suggest that down-regulation of B-Raf protein can contribute to motor neuron degeneration in SMA, pointing out a novel putative pathological mechanism that could be useful for developing new complementary SMN-independent therapies for SMA.
The results of this study have been published in the May issue of the high-profile journal PNAS.
For other information:
Prof. Stefania Corti, MD, PhD
Centro Dino Ferrari, Department of Pathophysiology and Transplantation
(DEPT), University of Milan, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
Tel. +39 02 55033817; firstname.lastname@example.org
Publication: Hensel N, Cieri F, Santonicola P, Tapken I, Schüning T, Taiana M, Pagliari E, Joseph A, Fischer S, Heidrich N, Brinkmann H, Kubinski S, Bergmann AK, Richter MF, Jung K, Corti S, Di Schiavi E, Claus P. Impairment of the neurotrophic signaling hub B-Raf contributes to motoneuron degeneration in spinal muscular atrophy. Proc Natl Acad Sci U S A. 2021 May 4;118(18):e2007785118. doi: 10.1073/pnas.2007785118. PMID: 33931501.