P2.083 Level of oxidative DNA damage and expression of apoptotic proteins in patients with Parkinson's disease treatment with L-dopa

Dorszewska, Jolanta; Florczak, Jolanta; Kozubski, Wojciech

doi:10.1016/s1353-8020(09)70434-1

Cited by 4 publications

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“…There are several hypotheses to explain the pathological processes in PD. One of them indicates the participation of oxidative stress in the damage that occurs to dopaminergic neurons [13][14][15]. In oxidative neuron damage, it is possible that impaired metabolism of homocysteine (Hcy) and other biothiols, such as methionine (Met), cysteine (Cys), and glutathione (GSH), may be involved.…”

Section: Oxidative Damage and Hyperhomocysteinemia And Biogenic Aminementioning

confidence: 99%

Introductory Chapter - Genetic and Biochemical Factors in Parkinson’s Disease

Dorszewska¹,

Kozubski²

2016

Challenges in Parkinson's Disease

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Section: Oxidative Damage and Hyperhomocysteinemia And Biogenic Aminementioning

confidence: 99%

Introductory Chapter - Genetic and Biochemical Factors in Parkinson’s Disease

Dorszewska¹,

Kozubski²

2016

Challenges in Parkinson's Disease

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“…The study of Dorszewska et al [ 8 ] indicates that the 8-oxo2dG levels are not significantly higher between 22 and 76 years of age, supporting the data from Alam et al [ 34 ] that shows that the level of oxidatively modified guanine in DNA is insignificantly higher in the brain of individuals between 43 and 91 years of age. The increase in the level of 8-oxo2dG was also demonstrated in the PBLs of patients with PD [ 65 , 67 ]. It is believed that the cause of the raised level of oxidatively modified nucleic acids in PD is both an overproduction of free radicals and a decrease in the level of enzymatic and non-enzymatic antioxidant repair systems [ 65 ].…”

Section: Influence Of L-dopa Treatment On the Level Of Oxidative Damamentioning

confidence: 99%

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment

Różycka

Jagodzińśki

Kozubski

et al. 2014

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An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease.

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“…However Alves Da Costa et al (2002) showed that -synuclein drastically lowered caspase-3 activity and p53 protein expression, and transcriptional activity, proteins controlled the apoptotic cascade. Blandini et al (2004), Dorszewska et al (2009b) and Iwashita (2004) showed that, apoptotic proteins such as: Bcl-2 family proteins and PARP are involved in the pathogenesis of PD as well.…”

Section: Influence Of L-dopa Treatment On the Level Of Apoptotic Factmentioning

confidence: 99%

Oxidative DNA Damage and the Level of Biothiols, and L-Dopa Therapy in Parkinson’s Disease

Dorszewska¹,

Kozubski²

2011

Etiology and Pathophysiology of Parkinson's Disease

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IntroductionParkinson'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-3,4dihydroxy-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 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., 2006Zoccolella et al., , 2009. 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. The most probably is that all factors are represented targets for PD therapy.

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P2.083 Level of oxidative DNA damage and expression of apoptotic proteins in patients with Parkinson's disease treatment with L-dopa

Cited by 4 publications

References 0 publications

Introductory Chapter - Genetic and Biochemical Factors in Parkinson’s Disease

Introductory Chapter - Genetic and Biochemical Factors in Parkinson’s Disease

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment

Oxidative DNA Damage and the Level of Biothiols, and L-Dopa Therapy in Parkinson’s Disease

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