Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for Parkinson's disease?
Parkinsonism (PD) is a neurodegenerative disorder of the brain resulting in dopamine deficiency caused by the progressive death of dopaminergic neurons. PD is characterized by a combination of rigidity, poverty of movement, tremor and postural instability. Selegiline is a selective and irreversible propargylamine type B monoamine oxidase (MAO-B) inhibitor. This drug, which inhibits dopamine metabolism, has been effectively used in the treatment of PD. However, its therapeutic effects are compromised by its many neurotoxic metabolites. To circumvent this obstacle, a novel MAO-B inhibitor, rasagiline, was developed. Paradoxically, the neuroprotective mechanism of propargylamines in different neuronal models appears to be independent of MAO-B inhibition. Recent investigations into the neuroprotective mechanism of propargylamines indicate that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), MAO-B and/or other unknown proteins may represent pivotal proteins in the survival of the injured neurons. Delineation of the mechanism(s) involved in the neuroprotective effects exerted by MAO-B inhibitors may provide the key to preventive novel therapeutic modalities.
Tabakman
Rinat
R
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Lecht
Shimon
S
Lazarovici
Philip
P
D000818:Animals; D017209:Apoptosis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000494:pharmacology; D008956:Models, Chemical; D008995:Monoamine Oxidase / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism; D010293:Pargyline / Q000031:analogs & derivatives* / Q000737:chemistry; D010300:Parkinson Disease / Q000188:drug therapy*; D011437:Propylamines / Q000737:chemistry; D013997:Time Factors
D004791:Enzyme Inhibitors; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D011437:Propylamines; C031967:rasagiline; C009054:propargylamine; D010293:Pargyline; D008995:Monoamine Oxidase