A retinoic acid receptor β agonist (CD2019) overcomes inhibition of axonal outgrowth via phosphoinositide 3-kinase signalling in the injured adult spinal cord

被引：45
作者：
Agudo, Marta [1 ]
Yip, Ping [1 ]
Davies, Meirion [1 ]
Bradbury, Elizabeth [1 ]
Doherty, Patrick [1 ]
McMahon, Stephen [1 ]
Maden, Malcolm [2 ]
Corcoran, Jonathan P. T. [1 ]
机构：
[1] Kings Coll London, Wolfson Ctr Age Related Dis, London SE1 1UL, England
[2] Kings Coll London, MRC Ctr Dev Neurobiol, London SE1 1UL, England
来源：
NEUROBIOLOGY OF DISEASE | 2010年 / 37卷 / 01期
基金：
英国惠康基金;
关键词：
OLFACTORY ENSHEATHING GLIA; NEURAL PROGENITOR CELLS; NERVE GROWTH-FACTOR; NEURITE OUTGROWTH; FUNCTIONAL RECOVERY; CORTICOSPINAL TRACT; GENE-TRANSFER; REGENERATION; PATHWAY; GAMMA;
D O I：
10.1016/j.nbd.2009.09.018
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
After spinal cord injury in the adult mammal, axons do not normally regrow and this commonly leads to paralysis. Retinoic acid (RA) can stimulate neurite outgrowth in vitro of both the embryonic central and peripheral nervous system. via activation of the retinoic acid receptor (RAR) beta 2 We show here that regions of the adult CNS. including the cerebellum and cerebral cortex, express RAR beta 2. We show that when cerebellar neurons are grown in the presence of myelin-associated glycoprotein (MAC) which inhibits neurite outgrowth, RAR beta can be activated in a dose dependent manner by a RAR beta agonist (CD2019) and neurite outgrowth can occur via phosphoinositide 3-kinase (PI3K) signalling. In a model of spinal cord injury CD2019 also acts through PI3K signalling to induce axonal outgrowth of descending corticospinal fibres and promote functional recovery Our data suggest that RAR beta agonists may be of therapeutic potential for human spinal cord injuries. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码：147 / 155
页数：9
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