Frataxin silencing alters microtubule stability in motor neurons: implications for Friedreich's Ataxia

Emanuela Piermarini, Daniele Cartelli, Anna Pastore, Giulia Tozzi, Claudia Compagnucci, Ezio Giorda, Jessica D’Amico, Stefania Petrini, Enrico Bertini E, Graziella Cappelletti and Fiorella Piemonte, Hum. Mol. Genet. (2016) doi: 10.1093/hmg/ddw260, First published online: August 11, 2016

We hypothesize that oxidative stress, determined by high GSSG levels, induces axonal retraction by interfering with MT dynamics. We propose a mechanism of the axonopathy in FRDA where GSSG overload and MT de-polymerization are strictly interconnected. Indeed, using a frataxin-silenced neuronal model we show a significant reduction of neurites extension, a shift of tubulin toward the unpolymerized fraction and a consistent increase of glutathione bound to the cytoskeleton.