title: Revelation in the neuroprotective functions of rasagiline and selegiline: the induction of distinct genes by different mechanisms.
abstract: In Parkinson's disease, cell death of dopamine neurons in the substantia nigra progresses and neuroprotective therapy is required to halt neuronal loss. In cellular and animal models, selegiline [(-)deprenyl] and rasagiline, inhibitors of type B monoamine oxidase (MAO)-B, protect neuronal cells from programmed cell death. In this paper, the authors review their recent results on the molecular mechanisms by which MAO inhibitors prevent the cell death through the induction of antiapoptotic, prosurvival genes. MAO-A mediates the induction of antiapoptotic bcl-2 and mao-a itself by rasagiline, whereas a different mechanism is associated with selegiline. Rasagiline and selegiline preferentially increase GDNF and BDNF in nonhuman primates and Parkinsonian patients, respectively. Enhanced neurotrophic factors might be applicable to monitor the neurorescuing activity of neuroprotection.
authors.affiliation: Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, Nisshin, Aichi, Japan. mnaoi@dpc.agu.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Naoi
authors.forename: Wakako
authors.initials: W
authors.lastname: Maruyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Inaba-Hasegawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000096:biosynthesis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy*; D012642:Selegiline / Q000494:pharmacology*
chemical_list: D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C031967:rasagiline; D012642:Selegiline; D008995:Monoamine Oxidase