Universität zu Köln

Joshi, Abhijeet R., Muke, Ines, Bobylev, Ilja and Lehman, Helmar C. (2019). ROCK inhibition improves axonal regeneration in a preclinical model of amyotrophic lateral sclerosis. J. Comp. Neurol., 527 (14). S. 2334 - 2341. HOBOKEN: WILEY. ISSN 1096-9861

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Abstract

Alteration of the RhoA/ROCK (Rho kinase) pathway has been shown to be neuroprotective in SOD1(G93A) mice, the most commonly used animal model of ALS. Since previous studies indicate that, apart from neuroprotection, ROCK inhibitor Y-27632 can also accelerate regeneration of motor axons, we here assessed the regenerative capability of axons in SOD1(G93A) mice with and without treatment with Y-27632. Regeneration of axons was examined after sciatic nerve crush in pre- and symptomatic SOD1(G93A) mice. Proregenerative effects of Y-27632 were studied during the disease course in the SOD1(G93A) mouse model. In symptomatic SOD1(G93A) mice, axonal regeneration was markedly reduced compared to presymptomatic SOD1(G93A) mice and wild types. Treatment with Y-27632 improved functional and morphological measures of motor axons after sciatic crush in all tested conditions. Y-27632 treatment did not increase the lifespan of symptomatic SOD1(G93A) mice, but did improve axonal (re)innervation of neuromuscular junctions. Our study provides proof of concept that axonal regeneration of motor neurons harboring SOD1(G93A) is impaired, but amenable for pharmacological interventions aiming to accelerate axonal regeneration. Given the lack of treatments for ALS, approaches to improve axonal regeneration, including by inhibiting ROCK, should be further explored.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Joshi, Abhijeet R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Muke, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED Bobylev, Ilja UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehman, Helmar C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-133479
DOI:	10.1002/cne.24679
Journal or Publication Title:	J. Comp. Neurol.
Volume:	527
Number:	14
Page Range:	S. 2334 - 2341
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1096-9861
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOTOR-NEURONS; DEGENERATION; FIBERS Multiple languages Neurosciences; Zoology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13347