Apoptotic mechanisms in neurodegeneration: possible relevance to glaucoma.
Deprenyl, a monoamine oxidase inhibitor used in the treatment of Parkinson's disease, along with its primary metabolite desmethyldeprenyl (DES) have been shown to reduce neuronal apoptosis by a mechanism that requires gene transcription and involves the maintenance of mitochondrial membrane potential. This review article explores the mechanisms by which DES maintains mitochondrial membrane potential. Mediated by GAPDH binding, DES increases mitochondrial BCL-2 and BCL-xL levels and decreases BAX levels thereby preventing the permeability transition pore (PTP) form opening and preventing apoptotic degradation. The favorable effects of deprenyl on neuronal apoptosis suggests the therapeutic potential of designing compounds with the capacity to alter the configurations of pro-apoptosis or anti-apoptotic proteins.
Tatton
W G
WG
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA. william_tatton@SMTPlink.mssm.edu
D000818:Animals; D017209:Apoptosis; D005901:Glaucoma / Q000378:metabolism / Q000503:physiopathology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009410:Nerve Degeneration / Q000503:physiopathology*; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D008996:Monoamine Oxidase Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D012642:Selegiline; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases