Oxidative stress in Parkinson’s disease

Jenner P. Oxidative stress in Parkinson s disease. Ann Neurol. 2003 53(suppl 3) S26-S38. 

Pennathur S, Jackson-Lewis V, Przedborski S, Heinecke JW (1999) Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and 0,0 -dityrosine in brain tissue of l-methyM-phenyl-1,2,3, 6-tetrahydropyridine-treated mice, a model of oxidative stress in Parkinson s disease. J Biol Chem 274 34621-34628. 

FIGURE 21.6 Oxidative stress in parkinson s disease. (From Taicco et al, 2004. Copyright 2004 with permission from Nature.)... 

Tsang, A.H. and Chung, K.K. (2009) Oxidative and nitrosative stress in Parkinson s disease. Eiochim. Biophys. Acta, 1792, 643-650. 

Similarly, abnormalities in the mitochondrial machinery and resulting oxidative stress may also intervene in Parkinson s disease (PD) [31, 32]. The decreased activity of mitochondrial complex I in PD patients [33], and the preferential toxicity of the complex I inhibitor rotenone [34] and MPP+ (the active metabolite of MPTP)... 

Ebadi M., Srinivasan S. K., and Baxi M. D. (1996). Oxidative stress and antioxidant therapy in Parkinson s disease. Prog. Neurobiol. 48 1-19. 

Several studies have explored SOD activity in peripheral tissues of patients with Parkinson s disease as potential markers of oxidative stress, and have yielded inconsistent results. Elevations of total (combined Cu,Zn-SOD and Mn-SOD) SOD activity and GSH peroxidase activity in serum of patients with Parkinson s disease have been reported. Furthermore, elevations of immunoreactive Mn-SOD in cerebrospinal fluid of patients with Parkinson s disease but normal levels of Cu,Zn-SOD have been detected. Erythrocyte SOD activity, which is exclusively due to Cu,Zn-SOD, is unaltered in Parkinson s disease. Moreover, no differences in mean activities of total SOD, GSH peroxidase, GSH reductase, or catalase have been detected in either the lymphocytes, granulocytes, or cerebrospinal fluid of patients with Parkinson s disease. 

The pathological characteristic of Parkinson s disease is the selective degeneration of dopamine neurons in the pars compacta of the substantia nigra. The mechanism for the loss of neurons remains to be elucidated, and recently apoptosis has been proposed as a death process in Parkinson s disease. For example, the level of a product of the oxidative stress, 4-hydroxy-2-nonenal protein adduct, was found to increase in the nigral neurons of parkinsonian brains. Peroxynitrite (see Figure 13.6) has been proposed to be involved in the neuronal cell death in some neurodegenerative diseases, such as amyotrophic lateral sclerosis. 

Fahn, S. and Cohen, G. 1992. The oxidant stress hypothesis in Parkinson s disease Evidence supporting it. Ann. Neurol. 32, 804-812. 

Increased levels of ROS due to oxidative stress have been consistently found in cardiovascular diseases as atherosclerosis or hypertension [18]. There is certain evidence that the free radicals involved in Parkinson s disease are mainly due to the production of increased levels of free radicals during oxidative metabolism of dopamine [19]. Oxidative stress, manifested by protein oxidation and lipid peroxidation (LP), among other alterations, is a characteristic of Alzheimer s disease [20] and in the pathogenesis of diabetes related complications. Treatment with antioxidants seemed to be a promising therapeutic option for these diseases [21], The inflammatory nature of rheumatoid arthritis implies that a state of oxidative stress may also exist in this disease [22,23]. Also, free radicals have a certain role in Huntington s disease [24,25], age related degeneration [26], and some autoimmune disorders [27],... 

Hald A, Lotharius J (2005) Oxidative stress and mflammation in Parkinson s disease Is there a causal link Exp Neurol 193 279-290. 

Although the exact cause of the progressive degeneration of nigrostriatal dopamine neurons in Parkinson s disease is still unknown, several mechanisms were proposed to explain the cell damaging processes at the molecular level that ultimately cause Parkinson s disease.127 These mechanisms, which are probably related by interacting mechanisms, include (1) excitotoxic mechanism, (2) mitochondrial toxins, and (3) oxidative stress. 

Parkinson s disease is caused by the oxidative stress-induced loss of dopaminergic neurons and can be effectively treated with levo-dopa in combination with dopa decarboxylase inhibitors such as carbidopa or catechoi-0-methyltransferase inhibitors such as tolca-pone. Levodopa is well known to increase the life spans of patients with Parkinson s disease. It may do this by enhancing brain dopamine levels and inhibiting tyrosine hydroxylase, which produces oxygen radicals. Several dopamine receptor agonists are available for use in Parkinson s disease and are extensively used in patients suffering from the adverse effects of levodopa. Anticholinergics such as trihexyphenidyl are also used in Parkinson s disease. 

Jenner, P., Dexter, D.T., Sian, J., Schapira, A.H.V. and Marsden. C.D. (1992) Oxidative stress as a cause of nigral cell death in Parkinson s disease and incidental Lewy body disease. Ann. Neurol. 32 (Suppl.) 82-87. 

In Parkinson s disease oxidative stress may play a principal role in the degeneration of dopaminergic neurones ... 

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