Enhancing aromatic L-amino acid decarboxylase activity: implications for L-DOPA treatment in Parkinson's disease.

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Hadjiconstantinou M, Neff NH

Enhancing aromatic L-amino acid decarboxylase activity: implications for L-DOPA treatment in Parkinson's disease.

CNS Neurosci Ther. 2008 Winter;14(4):340-51. doi: 10.1111/j.1755-5949.2008.00058.x.

PubMed ID

19040557 [ View in PubMed

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Abstract

Aromatic L-amino acid decarboxylase (AAAD) is an essential enzyme for the formation of catecholamines, indolamines, and trace amines. Moreover, it is a required enzyme for converting L-DOPA to dopamine when treating patients with Parkinson's disease (PD). There is now substantial evidence that the activity of AAAD in striatum is regulated by activation and induction, and second messengers play a role. Enzyme activity can be modulated by drugs acting on a number of neurotransmitter receptors including dopamine (D1-4), glutamate (NMDA), serotonin (5-HT(1A), 5-HT(2A)) and nicotinic acetylcholine receptors. Generally, antagonists enhance AAAD activity; while, agonists may diminish it. Enhancement of AAAD activity is functional, as the formation of dopamine from exogenous L-DOPA mirrors activity. Following a lesion of nigrostriatal dopaminergic neurons, AAAD in striatum responds more robustly to pharmacological manipulations, and this is true for the decarboxylation of exogenous L-DOPA as well. We review the evidence for parallel modulation of AAAD activity and L-DOPA decarboxylation and propose that this knowledge can be exploited to optimize the formation of dopamine from exogenous L-DOPA. This information can be used as a blue print for the design of novel L-DOPA treatment adjuvants to benefit patients with PD.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Levodopa	Aromatic-L-amino-acid decarboxylase	Protein	Humans	Unknown	Substrate	Details