''70th Birthday Professor Riederer'' induction of glial cell line-derived and brain-derived neurotrophic factors by rasagiline and (-)deprenyl: a way to a disease-modifying therapy?
Neuroprotection has been proposed in neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, to delay or halt disease progression or reverse neuronal deterioration. The inhibitors of type B monoamine oxidase (MAO), rasagiline and (-)deprenyl, prevent neuronal loss in cellular and animal models of neurodegenerative disorders by intervening in the death signal pathway in mitochondria. In addition, rasagiline and (-)deprenyl increase the expression of anti-apoptotic Bcl-2 protein family and neurotrophic factors. Neurotrophic factors, especially glial cell line-derived neurotrophic factor (GDNF) and brain-derived derived neurotrophic factor (BDNF), are required not only for growth and maintenance of developing neurons, but also for function and plasticity of distinct population of adult neurons. GDNF and BDNF have been reported to reduce Parkinson and Alzheimer's diseases, respectively. GDNF protects the nigra-striatal dopamine neurons in animal models of Parkinson's disease, and its administration has been tried as a disease-modifying therapy for parkinsonian patients. However, the results of clinical trials have not been fully conclusive and more practical ways to enhance GDNF levels in the targeted neurons are essentially required for future clinical application. Rasagiline and (-)deprenyl induced preferentially GDNF and BDNF in cellular and non-human primate experiments, and (-)deprenyl increased BDNF level in the cerebrospinal fluid of parkinsonian patients. In this paper, we review the induction of GDNF and BDNF by these MAO inhibitors as a strategy of neuroprotective therapy. The induction of prosurvival genes is discussed in relation to a possible disease-modifying therapy with MAO inhibitors in neurodegenerative disorders.
Department of Cognitive Brain Science, National Research Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.
Wakako
W
Maruyama
Makoto
M
Naoi
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D001523:Mental Disorders / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D012642:Selegiline