Open AccessPathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy
Author(s) -
Maria Elena Pero,
C Meregalli,
Xiangping Qu,
Grace Ji-eun Shin,
Atul Kumar,
Matthew Shorey,
Melissa M. Rolls,
Kurenai Tanji,
Thomas H. Brannagan,
Paola Alberti,
G Fumagalli,
L Monza,
Wesley B. Grueber,
Guido Cavaletti,
Francesca Bartolini
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2012685118
Subject(s) - bortezomib , peripheral neuropathy , tubulin , medicine , chemotherapy induced peripheral neuropathy , peripheral , microtubule , chemotherapy , axonal degeneration , cancer research , multiple myeloma , pathology , biology , endocrinology , microbiology and biotechnology , diabetes mellitus
Significance Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating “dying back” neuropathy featuring a distal-to-proximal peripheral nerve degeneration seen in cancer patients undergoing chemotherapy. The pathogenenic mechanisms of CIPN are largely unknown. We report that in sensory neurons, the CIPN-inducing drug bortezomib caused axonopathy and disrupted mitochondria motility by increasing delta 2 tubulin (D2), the only irreversible tubulin posttranslational modification and a marker of hyper-stable microtubules. These data provide a new paradigm for the risk associated with enhanced tubulin longevity in peripheral neuropathy and suggest that targeting the enzymes regulating this tubulin modification may provide therapies that prevent the axonal injury observed in bortezomib-induced peripheral neuropathy.