This proposal investigates the role of oligodendrocyte dysfunction and S100B signaling in ARSACS. The central hypothesis is that sacsin deficiency alters oligodendrocyte differentiation and function through dysregulation of S100B, a calcium-binding protein involved in myelination, neuroinflammation, cytoskeletal organization, and chaperone activity. The investigators propose to generate the first human oligodendrocyte model of ARSACS by directly reprogramming patient-derived fibroblasts into oligodendrocyte-like cells, characterize the effects of sacsin loss on oligodendrocyte biology, and determine whether manipulation of S100B expression or activity can rescue disease-associated phenotypes.
Subvention : $25 000
Durée : un an
Dr. Federico Herrera
Laboratory Head
Cell Structure and Dynamics Laboratory
Faculty of Sciences, University of Lisbon
Lisbonne, Portugal
Contact : fherrera@fc.ul.pt