期刊
JOURNAL OF COMPARATIVE NEUROLOGY
卷 527, 期 14, 页码 2334-2340出版社
WILEY
DOI: 10.1002/cne.24679
关键词
amyotrophic lateral sclerosis; axonal regeneration; rho kinase; RRID: IMSR_JAX: 002726; Y-27632
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据