Polymorphism of the COMT, MAO, DAT, NET and 5-HTT Genes, and Biogenic Amines in Parkinson’s Disease
Jolanta Dorszewska, Michal Prendecki, Anna Oczkowska, Agata Rozycka, Margarita Lianeri and Wojciech Kozubski
Affiliation: Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 49, Przybyszewskiego St. PL 60-355 Poznan, Poland.
Keywords: COMT, MAO, Monoamine transporters polymorphism, PD.
Epinephrine (E) and sympathetic nerve stimulation were described by Thomas Renton Elliott in 1905 for the
first time. Dopamine (DA), norepinephrine (NE), E, and serotonin (5-HT) belong to the classic biogenic amines (or monoamines).
Parkinson’s disease (PD) is among the diseases in which it has been established that catecholamines may account
for the neurodegeneration of central and peripheral catecholamine neural systems. PD is a chronic and progressive
neurological disorder characterized by resting tremor, rigidity, and bradykinesia, affecting 2% of individuals above the
age of 65 years. This disorder is a result of degeneration of DA-producing neurons of the substantia nigra and a significant
loss of noradrenergic neurons in the locus coeruleus. In PD and other related neurodegerative diseases, catecholamines
play the role of endogenous neurotoxins. Catechol-O-methyltransferase (COMT) and/or monoamine oxidase
(MAO) catalyze the metabolism of monoamines. However, the monoamine transporters for DA, NE, and 5-HT namely
DAT, NET, and SERT, respectively regulate the monoamine concentration. The metabolism of catecholamines and 5-HT
involves common factors. Monoamine transporters represent targets for many pharmacological agents that affect brain
function, including psychostimulators and antidepressants. In PD, polymorphisms of the COMT, MAO, DAT, NET, and 5-
HTT genes may change the levels of biogenic amines and their metabolic products. The currently available therapies for
PD improve the symptoms but do not halt the progression of the disease. The most effective treatment for PD patients is
therapy with L-dopa. Combined therapy for PD involves a DA agonist and decarboxylase, MAOs and COMT inhibitors,
and is the current optimal form of PD treatment maintaining monoamine balance.
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