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We thank Dr. R. Hishida, Dr. S. Muramatsu, and Dr. I. Nakano (Jichi Medical University, Department of Medicine, Division of Neurology), Dr. Y. Hirata (Gifu University, Faculty of Engineering, Department of Biomolecular Science), Dr. F. Imai (Fujita Health University, School of Medicine, Department of Neurosurgery), and Dr. M. Mogi (Aichi-Gakuin University, School of Pharmacy, Department of Medical Biochemistry) for their helpful advice and support of this work. Many of our studies described in this review were supported by grants-in-aid from the Ministry of Health, Labor, and Welfare of Japan (MS); Ministry of Education, Culture, Sports, Science, and Technology of Japan (MS); and Japan Health Sciences Foundation (MS).

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**16** 

*Poland* 

**Oxidative DNA Damage and the Level of** 

*Poznan University of Medical Sciences, Laboratory of Neurobiology Department of* 

Parkinson's disease (PD) is a chronic and progressive neurological disorder characterized by resting tremor, rigidity, and bradykinesia, affecting at least 1% of individuals above the age of 65 years. Parkinson's disease is a result of degeneration of the dopamine-producing neurons of the *substantia nigra*. Available therapies in PD will only improve the symptoms but not halt progression of disease. The most effective treatment for PD patients is therapy with L-3,4 dihydroxy-phenylalanine (L-dopa) (Olanow, 2008). As indicated in literature reports, L-dopa therapy leads to motor fluctuations and disabling involuntary movements called L-dopainduced dyskinesia (Carta et al., 2006; Obeso et al., 2008). Literature reports indicate also that long-term administration of L-dopa in PD patients may not only alter arginine (Arg) levels but may also lead to increased concentrations of homocysteine (Hcy), the factor responsible for development of atherosclerosis and dysfunction of nigral endothelial cells (Muller et al., 1999). Methylenetetrahydrofolate reductase (MTHFR) represents enzyme involved in remethylation of Hcy to methionine (Met). The C667T transition in *MTHFR* results in Ala>Val substitution in position 226 and, as a consequence, in 50 % decrease in the enzyme activity, and thus in an increased concentration of Hcy (Frosst et al., 1995). The study of Yasui et al. (2000) indicated that the TT genotype might be linked to pathogenesis of PD, particularly when the level of folates is low. Moreover, L-dopa metabolism via Omethylation by catechol-O-methyl-transferase (COMT) using S-adenosyl-L-methionine (SAM) leads to increase Hcy levels, hyper-Hcy (O'Suilleabhain et al., 2004a). A percentage 10-30% of PD patients exhibits hyper-Hcy. Hyper-Hcy in PD has been associated with affective and cognitive impairment, dementia, dyskinesia, and vascular disease

(O'Suilleabhain et al., 2004b; Rogers et al., 2003; Zoccolella et al., 2006, 2009).

The most probably is that all factors are represented targets for PD therapy.

The exact mechanism of development and progression of PD pathology is not clear. It is known, that a complex interplay of multiple environmental and genetic factors has been involved in pathogenesis of PD and it is possibly that PD represents rather a syndrome but not a single disorder. Moreover, is likely that in pathogenesis of PD there are several mechanisms involved, such as: oxidative stress, mitochondrial dysfunction, DNA damage, protein aggregation, neuroinflammation, excitotoxicity, apoptosis and loss of trophic factors.

**1. Introduction** 

**Biothiols, and L-Dopa Therapy in** 

Dorszewska Jolanta and Kozubski Wojciech

*Neurology, Chair and Department of Neurology,* 

**Parkinson's Disease** 

neurotoxicity: implications for Parkinson's disease. *FASEB J,* Vol. 16, No. 11, pp. 1474-1476.

