TY - JOUR T1 - Pathogenic Role of Delta 2 Tubulin in Bortezomib Induced Peripheral Neuropathy JF - bioRxiv DO - 10.1101/721852 SP - 721852 AU - Maria Elena Pero AU - Cristina Meregalli AU - Xiaoyi Qu AU - Atul Kumar AU - Matthew Shorey AU - Melissa Rolls AU - Kurenai Tanji AU - Thomas H. Brannagan AU - Paola Alberti AU - Giulia Fumagalli AU - Laura Monza AU - Guido Cavaletti AU - Francesca Bartolini Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/02/721852.abstract N2 - The pathogenesis of chemotherapy induced peripheral neuropathy (CIPN) is still poorly understood. Herein, we found that the CIPN-causing drug, bortezomib (Bort), induces delta 2 tubulin (D2) while affecting MT stability and dynamics in sensory neurons, and that accumulation of D2 is a hallmark of Bort-induced peripheral neuropathy in humans. Furthermore, while induction of D2 was sufficient to cause axonopathy and inhibit mitochondria motility, reducing D2 alleviated both axonal degeneration and loss of mitochondria motility promoted by Bort. Altogether, our data demonstrate that Bort, structurally unrelated to tubulin poisons, can affect the tubulin cytoskeleton in sensory neurons in vitro, in vivo and in humans, indicating that the pathogenic mechanisms of seemingly unrelated CIPN drugs may converge on tubulin damage. They further reveal a previously unrecognized pathogenic role for D2 in bortezomib-causing CIPN through its regulation of mitochondria dynamics. ER -