“Pathogenic Role of Tubulin Post Translational Modifications in Axon Degeneration"
Francesca Bartolini (Department of Pathology and Cell Biology, Columbia University, NY, USA)
Abstract
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 post-translational modification and a marker of hyperstable 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.
Francesca Bartolini is an Assistant Professor at Columbia University since 2013. Her research group at the Pathology & Cell Biology Department focuses on the understanding of the role of microtubule stability in the onset of neurodegeneration and peripheral neuropathy. Prof Bartolini has recently demonstrated that inhibition of microtubule dynamics and accumulation of tubulin post-translational modifications are driving factors for the induction of tau-mediated neuronal damage (Pianu et al., 2014 JCS; Qu et al., 2017 J Cell Biol) and developed novel microscopy assays that measure microtubule invasions into dendritic spines and single pre-synaptic boutons of cultured hippocampal, cortical neurons and in brain slices. Through this approach she has recently identified a novel subset of de novo nucleated microtubules at en passent boutons that are rate limiting for neuronal transmission (Qu et al., 2020 Curr Biol).
Venue: wednesday september 24th, 3.00 PM
https://meet.google.com/eqd-wwnd-zyn?hs=122&authuser=0
