Enzymatic stimulation and enzymatic inhibition in Parkinson's disease.
In order to supplement the deficient catecholamine neurotransmitters, dopamine and noradrenaline, in parkinsonian brains, the following strategies have been tried: (1) the precursor amino acids, L-DOPA and L-threo-dihydroxyphenylserine (DOPS), (2) 6R-L-erythro-tetrahydrobiopterin (BPH4) as tyrosine hydroxylase (TH) cofactor and nicotinamide adenine dinucleotide (NADH) as cofactor of dihydropteridine reductase to stimulate TH, (3) brain transplant of TH-containing cells, (4) inhibitors of monoamine oxidase (MAO) and/or catechol O-methyltransferase (COMT) with or without L-DOPA or L-DOPS, and (5) dopamine receptor agonists. Among these strategies, the precursor, L-DOPA, L-DOPS, MAO and COMT inhibitors, and dopamine receptor agonists have proved to be clinically effective. As a new strategy, increase in deficient TH activity has been tried experimentally and clinically either by stimulation of residual TH activity by the cofactors, BPH4 or NADH, or by brain transplant of natural TH-containing cells (fetal substantia nigra) or genetically engineered TH-containing cells.
Nagatsu
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Division of Molecular Genetics II Neurochemistry, School of Medicine, Fujita Health University, Aichi, Japan.
D000978:Antiparkinson Agents / Q000627:therapeutic use*; D065098:Catechol O-Methyltransferase Inhibitors; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004296:Dopa Decarboxylase / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D009638:Norepinephrine / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology*; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000502:physiology*
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D014446:Tyrosine 3-Monooxygenase; D004296:Dopa Decarboxylase; D004298:Dopamine; D009638:Norepinephrine