Kinesin-5 Blocker Monastrol Protects Against Bortezomib-Induced Peripheral Neurotoxicity

Neurotoxicity is a relevant side effect of bortezomib treatment. Previous reports have shown that the development of peripheral neuropathy caused by anti-neoplastic agents may be a result of reduced axonal transport. Based on evidence from prior studies that the kinesin-5 inhibitor monastrol enhance...

Full description

Saved in:
Bibliographic Details
Published in:Neurotoxicity research 2017-11, Vol.32 (4), p.555-562
Main Authors: Bobylev, Ilja, Peters, Dominik, Vyas, Maulik, Barham, Mohammed, Klein, Ines, von Strandmann, Elke Pogge, Neiss, Wolfram F., Lehmann, Helmar C.
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cell Biology
Neurobiology
Neurochemistry
Neurology
Neurosciences
Original Article
Pharmacology/Toxicology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Neurotoxicity is a relevant side effect of bortezomib treatment. Previous reports have shown that the development of peripheral neuropathy caused by anti-neoplastic agents may be a result of reduced axonal transport. Based on evidence from prior studies that the kinesin-5 inhibitor monastrol enhances axonal transport and improves neuronal regeneration, we focused on the neuroprotective role of monastrol during the chemotherapeutic treatment with bortezomib. Prolonged treatment of C57BL/6 mice with bortezomib induced a length-dependent small-fiber neuropathy with axonal atrophy and loss of sensory nerve fibers. The administration of monastrol substantially alleviated morphological features of axonal injury and functional measures of sensory neuropathy. Cytotoxicity studies in leukemia and multiple myeloma cell lines showed no interference of monastrol with the cytostatic effects of bortezomib. Our data indicate that the novel approach of targeting microtubule turnover by monastrol provides protection against bortezomib-induced neurotoxicity. The favorable cytotoxic profile of monastrol makes it an interesting candidate as neuroprotective agent in combined chemotherapy regimens that warrants further consideration.
ISSN:1029-8428
1476-3524
DOI:10.1007/s12640-017-9760-7