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, 15 (1), 11-7

Molecular Effects of L-dopa Therapy in Parkinson's Disease

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Molecular Effects of L-dopa Therapy in Parkinson's Disease

Jolanta Dorszewska et al. Curr Genomics.

Abstract

Parkinson's disease (PD) is one of the most common neurological diseases in elderly people. The mean age of onset is 55 years of age, and the risk for developing PD increases 5-fold by the age of 70. In PD, there is impairment in both motor and nonmotor (NMS) functions. The strategy of PD motor dysfunction treatment is simple and generally based on the enhancement of dopaminergic transmission by means of the L-dihydroxyphenylalanine (L-dopa) and dopamine (DA) agonists. L-dopa was discovered in the early -60's of the last century by Hornykiewicz and used for the treatment of patients with PD. L-dopa treatment in PD is related to decreased levels of the neurotransmitter (DA) in striatum and ab-sence of DA transporters on the nerve terminals in the brain. L-dopa may also indirectly stimulate the receptors of the D1 and D2 families. Administration of L-dopa to PD patients, especially long-time therapy, may cause side effects in the form of increased toxicity and inflammatory response, as well as disturbances in biothiols metabolism. Therefore, in PD pa-tients treated with L-dopa, monitoring of oxidative stress markers (8-oxo-2'-deoxyguanosine, apoptotic proteins) and in-flammatory factors (high-sensitivity C-reactive protein, soluble intracellular adhesion molecule), as well as biothiol com-pounds (homocysteine, cysteine, glutathione) is recommended. Administration of vitamins B6, B12, and folates along with an effective therapy with antioxidants and/or anti-inflammatory drugs at an early stage of PD might contribute to improvement in the quality of the life of patients with PD and to slowing down or stopping the progression of the disease.

Keywords: Biothiols; Immune response; L-dopa; Oxidative stress; PD..

Figures

Fig. (1)
Fig. (1)
Contribution of L-dopa in generation of oxidative stress and immunological response in PD. 3-OMD, 3-O-methyldopa; 8-oxo2dG, 8-oxo-2`-deoxyguanosine; AADC, aromatic amino acid decarboxylase; COMT, catechol-O-methyl transferase; Cys, cysteine; DA, dopamine; GSH, glutathione; Hcy, homocysteine; hs-CRP, high-sensitivity C-reactive protein; L-dopa, Ldihydroxyphenylalanine; Met, methionine; ox-LDL, oxidized low density lipoproteins; ROS, reactive oxygen species; SAH, Sadenosylhomocysteine; SAM, S-adenosylmethionine; sICAM, soluble intracellular adhesion molecule; TH, tyrosine hydroxylase. (↑) An increase and (↓) a decrease of biochemical parameters levels.

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