Abstract
(-)-Deprenyl ( L-deprenyl, selegiline hydrochloride), a selective monoamine oxidase B (MAO-B) inhibitor employed in the pharmacological therapy of Parkinson's disease, increases neuronal survival in both animal models of neurodegenerative disorders and acute CNS lesions. Despite intensive investigations, the mechanisms of (-)-deprenyl-mediated neuroprotection remain poorly understood. To test the hypothesis that (-)-deprenyl might have a beneficial effect not only on neuronal survival, but also on axonal regeneration, we describe here experiments performed in vitro and in vivo which clearly demonstrate that (-)-deprenyl fails to promote axonal regeneration of severed rat retinal ganglion cells (RGCs). Furthermore, (-)-deprenyl was not able to overcome free-radical-induced RGC axon degeneration. These results challenge the notion that (-)-deprenyl might be useful as a monotherapy for acute CNS lesions and give rise to a more critical viewpoint of the trophic-like function of this widely used therapeutic agent.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / drug effects*
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Brain-Derived Neurotrophic Factor / pharmacology
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Cell Survival / drug effects
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Free Radicals / toxicity
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GAP-43 Protein / biosynthesis
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Ganglia, Spinal / cytology
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Ganglia, Spinal / drug effects
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Ganglia, Spinal / growth & development
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Gene Expression Regulation / drug effects
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Genes, bcl-2 / genetics
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Immunohistochemistry
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In Vitro Techniques
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Male
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Molsidomine / analogs & derivatives*
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Molsidomine / pharmacology
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Monoamine Oxidase Inhibitors / pharmacology*
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Nerve Degeneration / chemically induced
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Nerve Degeneration / prevention & control
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Nerve Regeneration / drug effects*
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Neurites / drug effects
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Neuroprotective Agents / pharmacology*
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Optic Nerve / cytology
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Optic Nerve / drug effects
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Oxidative Stress / drug effects
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Rats
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Rats, Wistar
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Receptor, trkA / biosynthesis
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Receptor, trkB / biosynthesis
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Retinal Ganglion Cells / drug effects*
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Selegiline / pharmacology*
Substances
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Brain-Derived Neurotrophic Factor
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Free Radicals
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GAP-43 Protein
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Monoamine Oxidase Inhibitors
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Neuroprotective Agents
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Selegiline
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linsidomine
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Molsidomine
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Receptor, trkA
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Receptor, trkB