Universität zu Köln

Bobylev, Ilja, Peters, Dominik, Vyas, Maulik ORCID: 0000-0003-2996-4682, Barham, Mohammed, Klein, Ines, von Strandmann, Elke Pogge, Neiss, Wolfram F. and Lehmann, Helmar C. (2017). Kinesin-5 Blocker Monastrol Protects Against Bortezomib-Induced Peripheral Neurotoxicity. Neurotox. Res., 32 (4). S. 555 - 563. NEW YORK: SPRINGER. ISSN 1476-3524

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bobylev, Ilja UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Vyas, Maulik UNSPECIFIED orcid.org/0000-0003-2996-4682 UNSPECIFIED Barham, Mohammed UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED von Strandmann, Elke Pogge UNSPECIFIED UNSPECIFIED UNSPECIFIED Neiss, Wolfram F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Helmar C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-213778
DOI:	10.1007/s12640-017-9760-7
Journal or Publication Title:	Neurotox. Res.
Volume:	32
Number:	4
Page Range:	S. 555 - 563
Date:	2017
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1476-3524
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MULTIPLE-MYELOMA; TUBULIN POLYMERIZATION; AXONAL-TRANSPORT; SENSORY NEURONS; GROWING AXONS; NEUROPATHY; INHIBITION; REGENERATION; CELLS; PROTEASOME Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21377