PMID- 17447416
OWN - NLM
STAT- MEDLINE
DCOM- 20070517
LR  - 20191026
IS  - 0303-6995 (Print)
IS  - 0303-6995 (Linking)
IP  - 71
DP  - 2006
TI  - Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to 
      Parkinson's disease: possible implications of glial cells.
PG  - 53-65
AB  - Monoamine oxidases A and B (MAO A and MAO B) are the major enzymes that catalyze 
      the oxidative deamination of monoamine neurotaransmitters such as dopamine (DA), 
      noradrenaline, and serotonin in the central and peripheral nervous systems. MAO B 
      is mainly localized in glial cells. MAO B also oxidizes the xenobiotic 
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to a parkinsonism-producing 
      neurotoxin, 1-methyl-4-phenyl-pyridinium (MPP+). MAO B may be closely related to 
      the pathogenesis of Parkinson's disease (PD), in which neuromelanin-containing DA 
      neurons in the substantia nigra projecting to the striatum in the brain 
      selectively degenerate. MAO B degrades the neurotransmitter DA that is deficient 
      in the nigro-striatal region in PD, and forms H2O2 and toxic aldehyde metabolites 
      of DA. H2O2 produces highly toxic reactive oxygen species (ROS) by Fenton 
      reaction that is catalyzed by iron and neuromelanin. MAO B inhibitors such as 
      L-(-)-deprenyl (selegiline) and rasagiline are effective for the treatment of PD. 
      Concerning the mechanism of the clinical efficacy of MAO B inhibitors in PD, the 
      inhibition of DA degradation (a symptomatic effect) and also the prevention of 
      the formation of neurotoxic DA metabolites, i.e., ROS and dopamine derived 
      aldehydes have been speculated. As another mechanism of clinical efficacy, MAO B 
      inhibitors such as selegiline are speculated to have neuroprotective effects to 
      prevent progress of PD. The possible mechanism of neuroprotection of MAO B 
      inhibitors may be related not only to MAO B inhibition but also to induction and 
      activation of multiple factors for anti-oxidative stress and anti-apoptosis: 
      i.e., catalase, superoxide dismutase 1 and 2, thioredoxin, Bcl-2, the cellular 
      poly(ADP-ribosyl)ation, and binding to glyceraldehydes-3-phosphate dehydrogenase 
      (GAPDH). Furthermore, it should be noted that selegiline increases production of 
      neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic 
      factor (BDNF), and glial cell line-derived neurotrphic factor (GDNF), possibly 
      from glial cells, to protect neurons from inflammatory process.
FAU - Nagatsu, T
AU  - Nagatsu T
AD  - Department of Pharmacology, School of Medicine, Fujita Health University, 
      Toyoake, Aichi, Japan. tnagatsu@fujita-hu.ac.jp
FAU - Sawada, M
AU  - Sawada M
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Austria
TA  - J Neural Transm Suppl
JT  - Journal of neural transmission. Supplementum
JID - 0425126
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Monoamine Oxidase/*genetics/metabolism
MH  - Monoamine Oxidase Inhibitors/*therapeutic use
MH  - Parkinson Disease/*drug therapy/*enzymology
RF  - 153
EDAT- 2007/04/24 09:00
MHDA- 2007/05/18 09:00
CRDT- 2007/04/24 09:00
PHST- 2007/04/24 09:00 [pubmed]
PHST- 2007/05/18 09:00 [medline]
PHST- 2007/04/24 09:00 [entrez]
AID - 10.1007/978-3-211-33328-0_7 [doi]
PST - ppublish
SO  - J Neural Transm Suppl. 2006;(71):53-65. doi: 10.1007/978-3-211-33328-0_7.