Selegiline dopaminergic neuron protection

Selegiline inhibits the activity of monoamine B, enhances the release of dopamine, blocks the uptake of dopamine, is a calmodulin antagonist, and enhances the level of cyclic AMP, which in turn protects dopaminergic neurons. 

Selegiline protects dopaminergic neurons from glutamate-induced exatatoxicity. 

Selegiline increases the striatal superoxide dismutase, protects against peroxynitrite- and nitric-oxide-induced apoptosis, and guards dopaminergic neurons from toxicity induced by glutathione depletion. 

PROTECTION BY SELEGILINE OF DOPAMINERGIC NEURONS IN CULTURE FROM TOXIC FACTORS... 

In addition to MPTP, other endogenously produced neurotoxins, namely, the monoamine-derived 1,2,3,4-tetrahydroisoquinolines and 6,7-dihydroxy-l,2,3,4-tetrahydroisoquinolines, have been proposed as factors accelerating dopamine cell death. A-methylated isoquinolines were found to be oxidized by MAO, and hydroxyl radicals were found to be produced by this reaction. In addition, by incubation with the A-methylated isoquinolines, ATP was depleted from a dopaminergic cell model. Pretreatment of the cells with MAO inhibitors such as selegiline could, however, protect against ATP depletion. These results suggest that oxidation of neurotoxic isoquinolines is directly involved in the oxidative stress to induce the cell death of dopamine neurons. On the other hand, 1 -methyl-1,2,3,4-tetrahydroisoquinoline and 1 -methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquino-... 

The neuroprotection of SH-SY54 cells from apoptosis caused by NOR-4 and SIN-1 is not related to inhibition of MAO-B, because SH-SY54 contains only MAO-A. Selegiline is able to protect dopaminergic neurons from the toxicity of MPTP and also of MPP an oxidized product of MPTP by MAO-B. This indicates that the neuroprotection by selegiline does not require blockage of the conversion of MPTP to MPP+. 

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