Invited Talk

Role of microtubules in axonal degeneration caused by chemotherapeutic agents

Soft Condensed Matter Group, Raman Research Institute, Bangalore—560 080, India

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Chemotherapy-induced peripheral neuropathy (CIPN) occurs as a serious side effect to treatment using antineoplastic agents, often forcing discontinuation of an otherwise successful therapy. Despite decades of work on drug development, and the availability of several drugs with different modes of action, CIPN continues to be a vexing problem. A major reason for this is our lack of mechanistic understanding of the nerve degeneration process, which involves cytoskeletal, mitochondrial, and ion-channel gating dysfunctions. CIPN sets in from the longest of axons that innervate the limbs, suggesting that the axonal microtubule skeleton, which is responsible for long-distance transport, may be a major causative element in the degeneration pathway. With this hypothesis, we investigate the correlation between microtubule stability and axonal stability. In this talk we’ll discuss some methods we have developed to investigate this and some recent results.