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Counteraction of axonal growth inhibitory properties of Semaphorin 3A and myelin-associated proteins by a synthetic neurotrophic compound
被引:13
|作者:
Hanbali, M
Bernard, F
Berton, C
Gatineau, G
Perraut, M
Aunis, D
Luu, B
Bagnard, D
机构:
[1] Ctr Neurochim, INSERM, U575, F-67084 Strasbourg, France
[2] Ctr Neurochim, Lab Chim Organ Subst Nat, CNRS, ULP UMR7123, F-67084 Strasbourg, France
关键词:
axon;
cortex;
myelin;
neurotrophic factor;
regeneration;
Semaphorin;
D O I:
10.1111/j.1471-4159.2004.02601.x
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
One of the reasons for the lack of nerve regeneration in the CNS is the formation of a glial scar over-expressing multiple inhibitory factors including myelin-associated proteins and members of the Semaphorin family. Innovative therapeutic strategies must stimulate axon extension across the lesion site despite this inhibitory molecular barrier. We recently developed a synthetic neurotrophic compound combining an omega-alkanol with a retinol-like cycle (3-(15-hydroxy-pentadecyl)-2,4,4,-trimethyl-cyclohexen-2-one (tCFA15)). Here, we demonstrate that tCFA15 is able to promote cortical axon outgrowth in vitro even in the presence of the inhibitory Semaphorin 3A and myelin extracts. This growth-promoting effect is selectively observed in axons and requires multiple growth-associated intracellular pathways. Our results illustrate the potential use of synthetic neurotrophic compounds to promote nerve regeneration by counteracting the axonal growth inhibition triggered by glial scar-associated inhibitory factors.
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页码:1423 / 1431
页数:9
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