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Table of Contents    
COMMENTARY
Year : 2017  |  Volume : 65  |  Issue : 2  |  Page : 269-270

Oxidative stress and Parkinson's disease


Department of Neurology, P D Hinduja National Hospital and Medical Research Center, V Savarkar Marg, Mahim, Mumbai, Maharashtra, India

Date of Web Publication10-Mar-2017

Correspondence Address:
Charulata Savant Sankhla
Department of Neurology, P D Hinduja National Hospital and Medical Research Center, V Savarkar Marg, Mahim, Mumbai - 400 016, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.201842

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How to cite this article:
Sankhla CS. Oxidative stress and Parkinson's disease. Neurol India 2017;65:269-70

How to cite this URL:
Sankhla CS. Oxidative stress and Parkinson's disease. Neurol India [serial online] 2017 [cited 2017 Mar 25];65:269-70. Available from: http://www.neurologyindia.com/text.asp?2017/65/2/269/201842


Parkinson's disease (PD) occurs due to a slow and progressive degeneration of dopaminergic neurons in the substantia nigra. The origin of this cell death is not known but involves an interplay between genes, possibly environmental toxins and endogenous factors. The endogenous factors that contribute to cell death are dopamine, interaction between dopamine and a- synuclein, and autonomous firing of substantia nigra cells using calcium ions to trigger action potentials. This, in turn, leads to oxidative stress, accumulation of proteins, deficit in mitochondrial complex 1 and neuroinflammatory processes leading to the apoptosis cascade and subsequent cell death. Microglial activation and an infiltration of lymphocytes are seen in the cerebral parenchyma of patients with PD, which supports the implication of the neuroinflammatory process in cell death.

Although the initiation of cell death is not understood, various postulates involved in the pathogenesis seem to be converging to the above events. It is now recognized that various PD-linked genes can directly or indirectly affect the mitochondrial dysfunction.

Amongst various pathogenetic mechanisms proposed in the pathogenesis of PD, oxidant stress secondary to dopamine metabolism has been on the forefront. Oxygen free radicals produced during the normal dopamine metabolism are toxic. It has been postulated that PD patients have a generalized, systemic defect in oxidative metabolism. This causes an increased production of oxygen free radicals in the presence of inadequate protective mechanisms.

We now know with emphasis on non-motor symptoms seen in PD that the pathogenesis of PD extends beyond the substantia nigra and also beyond the central nervous system.[1] There are various suggestions that point to Parkinson's disease being a systemic disorder with its pathology extending beyond the brain or the nervous system. For example, skin ailments such as seborrhoea and weight loss are common in PD patients. Investigators are now looking at biochemical abnormalities beyond the central nervous system, preferably in the serum or the cerebrospinal fluid (CSF), to diagnose PD or to recognize it before the onset of motor systems. Mitochondrial oxidative phosphorylation abnormalities are detected in substantia nigra, in platelets, and in the muscle of patients with PD.[2]

Malondialdehyde is a product of injury to the lipid membrane due to the action of oxygen free radicals. Excessive concentrations of the lipid peroxidation product, malondialdeyde, is seen in the substantia nigra following post-mortem examination conducted on the brains of PD patients.[3] Since the disease pathology in PD extends beyond the central nervous system, evidence of oxidative stress has also been demonstrated outside the brain. Increased concentration of malondialdehyde has been demonstrated in the sera and plasma of PD patients in two independent studies.[4],[5]

The detection of elevated serum malondialdehyde in the sera or plasma of PD patients, if proven, would provide us with a disease marker. In a study by Ahlskog et al., the serum malondialdehyde levels were checked in five groups of patients with PD, namely, those who were on levodopa, those in whom PD was left untreated, the normal controls, the patients suffering from Alzheimer's disease, and the patients suffering from diabetic mellitus.[6] No significant difference was noted in the serum malondialdehyde level in the first four groups, but the serum malondialdehyde level was elevated in diabetic patients. Similar results were seen by another group of investigators.[7] Serum malondialdehyde is also elevated in congestive heart failure and in the presence of mitochondrial myopathies. These studies have, therefore, shown that serum malondialdehyde might not be such a specific marker by itself. In the paper in focus, by Naduthota et al., the combination of voxel based morphometry and serum malondialdehyde levels have yielded more specific results, especially since they are assessed in a large and selective group of PD patients.[8]

Imaging biomarkers are now widely used in various neurological diseases. Voxel-based morphometry (VBM) is a quantitative magnetic resonance imaging (MRI) technique that is used to show in vivo neuropathological changes in the neurological brain. It has been widely used in neuropsychiatric disorders and in neurological disorders including PD and PD dementia. Many studies have shown an increased progression of brain atrophy in PD patients when compared with normal controls; however, there has been no uniform conclusion on the gray matter atrophy in the cortical and subcortical regions in patients with PD across these studies, due to the small and heterogeneous population of patients recruited in these studies, as well as the use of different imaging protocols.[9]

 
  References Top

1.
Ravan A, Ahmad FM, Chabria S, Gadhari M, Sankhla CS. Non-motor symptoms in an Indian cohort of Parkinson's disease patients and correlation of progression of non-motor symptoms with motor worsening Neurol India. 2015;63:166-74  Back to cited text no. 1
    
2.
Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD. Mitochondria1complex I deficiency in Parkinson's disease. Lancet 1989;1:1269.   Back to cited text no. 2
    
3.
Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, Jenner P, Marsden CD. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem 1989;52:381-389.  Back to cited text no. 3
    
4.
Kilinç A, Yalçin AS, Yalçin D, Taga Y, Emerk K. Increased erythrocyte susceptibility to lipid peroxidation in human Parkinson's disease. Neurosci Lett 1988;87:307-3.  Back to cited text no. 4
    
5.
Kalra J, Rajput AH, Mantha SV, Chaudhary AK, Prasad K. Oxygen free radical producing activity of polymorphonuclear leukocytes in patients with Parkinson's disease. Mol Cell Biochem1992;112:181-6.  Back to cited text no. 5
    
6.
Ahlskog JE, Uitti RJ, Low PA, Tyce GM, Nickander KK, Petersen RC, Kokmen E. No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease. Mov Disord 1995;10:566-73.  Back to cited text no. 6
    
7.
Molina JA, Jiménez-Jiménez FJ, Fernandez-Calle P, Lalinde L, Tenias JM, PondalM, et al. Serum lipid peroxides in patients with Parkinson's disease. Neurosci Lett 1992;136:137-40.  Back to cited text no. 7
    
8.
Naduthota RM, Bharath RD, Jhunjhunwala K, Yadav R, Saini J, Christopher R, Pal PK. Imaging biomarker correlates with oxidative stress in Parkinson's disease. Neurol India 2016;65:263-268.  Back to cited text no. 8
    
9.
Pan PL, Song W, Shang HF. Voxel-wise meta-analysis of gray matter abnormalities in idiopathic Parkinson's disease. Eur J Neurol 2012; 19:199-206.  Back to cited text no. 9
    




 

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