Paclitaxel Reduces Axonal Bclw to Initiate IP₃R1-Dependent Axon Degeneration.

ABSTRACT: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of many cancer treatments. The hallmark of CIPN is degeneration of long axons required for transmission of sensory information; axonal degeneration causes impaired tactile sensation and persistent pain. Currently the molecular mechanisms of CIPN are not understood, and there are no available treatments. Here we show that the chemotherapeutic agent paclitaxel triggers CIPN by altering IP₃ receptor phosphorylation and intracellular calcium flux, and activating calcium-dependent calpain proteases. Concomitantly paclitaxel impairs axonal trafficking of RNA-granules and reduces synthesis of Bclw (bcl2l2), a Bcl2 family member that binds IP₃R1 and restrains axon degeneration. Surprisingly, Bclw

SUBMITTER: Pease-Raissi SE 

PROVIDER: S-EPMC5680044 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature