Neurochemical perspectives to the function of monoamine oxidase.
Dopamine (DA) is degraded in part by MAO, an intraneuronal and glial enzyme localized at the outer mitochondrial membrane. DA is a good substrate for MAO-B and selegiline enhances DA-transmission and improves akinesia of Parkinson's disease (PD) by selective MAO-B blockade. Immunocytochemistry (ICC) and histochemistry (HC) demonstrate that neurons of substantia nigra (SN) lack MAO near totally (but see Moll et al 1988). Consequently, inhibition of MAO-B in this brain area occurs mainly in glial cells. Therefore an increase of DA in glia seems to be of long-lasting therapeutic benefit in PD. In addition, synthesis of hydrogen peroxide generated via MAO-B is blocked by selegiline. By this toxicity by endogenous free radicals is diminished. Furthermore, exogenous neurotoxicity by MAO-B substrates can be prevented by inhibition of MAO-B, while such MAO-A substrates are metabolized at the level of the MAO-A containing endothelium of capillaries. As conclusion, selegiline is a safe inhibitor of MAO-B that reduces neurotoxicity possibly triggering PD. (Table: see text).
Riederer
P
P
Dept. Psychiatry, University of Würzburg, FRG.
Konradi
C
C
Hebenstreit
G
G
Youdim
M B
MB
D001921:Brain / Q000201:enzymology*; D006801:Humans; D008125:Locus Coeruleus / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology*; D010300:Parkinson Disease / Q000201:enzymology; D011903:Raphe Nuclei / Q000201:enzymology; D013378:Substantia Nigra / Q000201:enzymology
D008995:Monoamine Oxidase