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Neurochemical perspectives to the function of monoamine oxidase
Author(s) -
Riederer P.,
Konradi C.,
Hebenstreit G.,
Youdim M.B.H.
Publication year - 1989
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1989.tb01781.x
Subject(s) - selegiline , monoamine oxidase b , monoamine oxidase , substantia nigra , neurochemical , neurotoxicity , chemistry , dopamine , pharmacology , biochemistry , medicine , neuroscience , parkinson's disease , enzyme , toxicity , biology , dopaminergic , disease , organic chemistry
– 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‐BICC HC ICC HCDRN • — +++ +++ 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