Multiple pathological mechanisms are involved in the development of chemotherapy-induced peripheral neurotoxicity (CIPN). Recent work has provided insights into the molecular mechanisms underlying chemotherapy-induced axonal degeneration. This review integrates evidence from preclinical and clinical …

2017年8月31日 · Chemotherapy-induced peripheral neuropathy (CIPN) is a common and enduring disorder caused by several anti-neoplastic agents. CIPN typically presents with neuropathic pain, numbness of distal extremities, and/or oversensitivity to …

This review integrates evidence from preclinical and clinical work on the onset, progression and outcome of axonal degeneration in CIPN. We review likely triggers of axonal degeneration in CIPN and highlight evidence of molecular pathways involved in axonal degeneration and their relevance to CIPN, including SARM1-mediated axon degeneration ...

2022年2月7日 · Calcium dysregulation constitutes a critical event in CIPN, but it is not known how chemotherapies such as paclitaxel alter intra-axonal calcium and cause degeneration. Here, we demonstrate that paclitaxel triggers Sarm1-dependent cADPR production in distal axons, promoting intra-axonal calcium flux from both intracellular and extracellular ...

2021年11月29日 · Preclinical evidence indicates that activation of the Wallerian-like degeneration pathway driven by sterile alpha and TIR motif containing 1 (SARM1) is responsible for axonopathy in CIPN. SARM1 is the central driver of an evolutionarily conserved programme of axonal degeneration downstream of chemical, inflammatory, mechanical or metabolic ...

2018年8月16日 · Current study aims to realize clinical benefits of neurorestorative therapy targeting neuronal survival and axon integrity in a mouse model of CIPN. These findings form the basis of our hypothesis that forced expression of human Hsp27 (hHsp27) rendered CIPN with paclitaxel protects peripheral neurons and fibers from progressive degeneration.

We review likely triggers of axonal degeneration in CIPN and highlight evidence of molecular pathways involved in axonal degeneration and their relevance to CIPN, including SARM1- mediated axon degeneration pathway.

Using organs-on-chip with Oxaliplatin agent in CIPN applications. Oxaliplatin, a platinum agent, disrupts DNA through crosslinking, inhibiting replication. The major hallmark of CIPN neuropathology is a “dying back” axon degeneration that proceeds in a distal-to-proximal fashion.

Chemotherapy-induced peripheral neuropathy (CIPN) affects 30–70% of chemotherapy patients, depending on the administered drug. Intriguingly, intense research efforts point to remarkably similar causes of axon degeneration, regardless of the type of drug that is administered.

Mechanisms of cellular injury related to CIPN include axon degeneration, dysregulation of calcium homeostasis, mitochondrial damage, and reactive oxygen species formation initiated by several factors (e.g., DNA damage from chemotherapy). Targeting Programmed Axon Degeneration in CIPN. Axonal degeneration is a well-described hallmark of CIPN ...