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- Title
Counteraction of axonal growth inhibitory properties of Semaphorin 3A and myelin-associated proteins by a synthetic neurotrophic compound.
- Authors
Hanbali, Mazen; Bernard, Frédéric; Berton, Caroline; Gatineau, Gilles; Perraut, Martine; Aunis, Dominique; Luu, Bang; Bagnard, Dominique
- Abstract
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 w-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.
- Subjects
AXONS; MYELIN proteins; MYELIN sheath; NERVE tissue proteins; NEUROTROPHIC functions; REGENERATION (Biology)
- Publication
Journal of Neurochemistry, 2004, Vol 90, Issue 6, p1423
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2004.02601.x