Kinome profiling in progressive multiple sclerosis using bone marrow-derived mesenchymal stromal cells

<h3></h3> Post-translational phosphorylation by protein kinases plays critical roles in cell-signalling, - survival, -differentiation and apoptosis. The kinome is the complete set of protein kinases encoded in the genome and, of the currently documented 518 protein kinases, 244 map to disease loci. Indeed, aberrant phosphorylation and protein accumulation is a hallmark of several neurodegenerative diseases. In multiple sclerosis (MS), large protein aggregates composed primarily of amyloid precursor protein and hypo- or hyper- phosphorylated neurofilaments are understood to contribute to axonal atrophy and neuronal loss. Bruton’s tyrosine kinase inhibitors are promising disease modifying agents for MS, including for progressive disease. However, total kinase activity remains understudied in MS. Using PamChip® array to measure total protein kinase activity in bone marrow-derived mesenchymal stromal cells, we identified a panel of over 80 kinases with differential activity in progressive MS. Here, we report these and how they map to potential pathophysiological processes in progressive MS. We also describe how, with additional interrogation of the pathways involved, these findings have potential to identify novel biomarkers and therapeutic interventions in progressive MS.