Title:Role of Catechol-O-Methyltransferase (COMT)-Dependent Processes in Parkinson’s Disease and L-DOPA Treatment
VOLUME: 11 ISSUE: 3
Author(s):Stefano Espinoza, Francesca Manago, Damiana Leo, Tatyana D. Sotnikova and Raul R. Gainetdinov
Affiliation:Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Morego 30, Genova, Italy.
Keywords:Dyskinesia, 3-methoxytyramine, trace amines, TAAR1, tolcapone, entacapone, nebicapone, Catechol O Methyl Transferase, Dyskinesia, L-DOPA, COMT, COMT Inhibitors, Parkinson's disease
Abstract:One of the most important enzymes in the catecholamine cycle, catecholamine-O-methyltransferase (COMT),
plays a critical role in the extracellular metabolism of dopamine and norepinephrine both in the periphery and the central
nervous system. COMT has attracted strong interest in regards to its role in dopamine-related pathologies, particularly
Parkinson’s disease. There are several mechanisms for the potential involvement of COMT-related processes in the
pathophysiology of Parkinson’s disease or the consequences of L-DOPA treatment. COMT-mediated metabolism of LDOPA
in the periphery influences brain dopamine levels, while the product of central COMT-mediated dopamine
metabolism, 3-methoxytyramine, can affect movement via interaction with Trace Amine-Associated Receptor 1
(TAAR1). COMT inhibitors have a long history of clinical use in the treatment of Parkinson’s disease. Several clinical
genetic studies have shown that variants of COMT gene contribute to the manifestations or treatment responses of this
disorder. Here, we review the basic molecular mechanisms that could be involved in COMT-dependent processes in
Parkinson’s disease, the pharmacological properties of COMT inhibitors used in the treatment of this disorder and the
clinical genetic observations involving COMT gene variants as modulators of pathological processes and responses to
dopamine replacement therapies used in the treatment of the disorder.
