Neurochemical perspectives to the function of monoamine oxidase

Abstract

– Dopamine (DA) is degradated 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. Brain area MAO-A MAO-B ICC HC ICC HC DRN • — +++ +++ LC +++ +++ — — SN —(+10%)' — — — Astroglia +++ + +++ +++ — without reaction or staining + mild reaction; +++ intensive reaction or staining; DRN dorsal raphe nucleus; LC locus coeruleus; 'Moll et al. 1988