Parkinson’s Disease—Apoptosis and Dopamine Oxidation

Abstract

Tyrosine hydroxylase, monoamine oxidase and aldehyde dehydrogenase all form oxygen radicals as part of their mechanisms of action. These oxygen radicals damage dopaminergic neurons in the substantianigra of the midbrain and cause them to die by a process of necrosis or apoptosis. Oxygen radicals quickly abstract hydrogen from DNA forming DNA radicals and causing DNA fragmentation, activation of DNA protective mechanisms, NAD depletion and cell death. Tyrosine hydroxylase is present in all dopaminergic neurons, is involved in the synthesis of dopamine and forms oxygen radicals in a redox mechanism involving its cofactor, tetrahydrobiopterin. Levodopa is used therapeutically in Parkinson's disease patients since it is a precursor for dopamine, an inhibitor of tyrosine hydroxylase, and prolongs patient's lives. Monoamine oxidase converts dopamine into 3,4-dihydroxyphenylacetaldehyde and forms oxygen radicals.Aldehyde dehydrogenase oxidizes the aldehyde and forms oxygen radicals and 3,4-dihydroxyphenylacetic acid. The treatment of Parkinson's disease should involveinhibitors of oxygen radical formation in dopaminergic neurons and neuroprotective agents that stimulate DNA repair and prevent cell death.

Possible causes of Parkinson’s disease

“…By the time symptoms appear, 50-90% of the dopaminergic neurons in the substantia nigra have been lost. Dopamine has a propensity to oxidize in processes that produce oxygen radicals [2][3][4]. This oxidative stress damages dopaminergic neurons and causes a progressive, age related loss of these neurons.…”