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Antioxidants (Basel). 2017 Jul 10;6(3). pii: E51. doi: 10.3390/antiox6030051.

Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress.

Author information

1
Cellular and Molecular Research Center, Shahrekord University of Medical Science, Shahrekord 88157, Iran. Fereshte.ahmadi86@ymail.com.
2
Department of Biological Sciences, St John's University, New York, NY 11439, USA. mollers@stjohns.edu.
3
Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger 4068, Norway. mollers@stjohns.edu.
4
Cellular and Molecular Research Center, Shahrekord University of Medical Science, Shahrekord 88157, Iran. mchalesh@yahoo.com.
5
SciLifeLab, KTH Royal Institute of Technology, Solna 17165, Sweden. gholamreza.bidkhori@scilifelab.se.
6
Cellular and Molecular Research Center, Shahrekord University of Medical Science, Shahrekord 88157, Iran. sjamif@gmail.com.

Abstract

Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson's disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS). Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. The former includes a number of enzymes such as catalase and glutathione peroxidase, while the latter contains a number of antioxidants acquired from dietary sources including vitamin C, carotenoids, flavonoids and polyphenols. There are also scavengers used for therapeutic purposes, such as 3,4-dihydroxyphenylalanine (L-DOPA) used routinely in the treatment of Parkinson's disease (not as a free radical scavenger), and 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) that acts as a free radical detoxifier frequently used in acute ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against oxidative stress conditions rely on the alteration of a number of stress proteins such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1). Although they share the targets in reversing the cytotoxic effects of H₂O₂, they seem to have distinct mechanism of function. Exposure to L-DOPA may result in hypoxia condition and further induction of ORP150 (150-kDa oxygen-regulated protein) with its concomitant cytoprotective effects but Edaravone seems to protect cells via direct induction of Peroxiredoxin-2 and inhibition of apoptosis.

KEYWORDS:

Edaravone; L-DOPA; neurodegenerative disease; oxidative stress; proteomics

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