These proteins, including PINK1 (PTEN-induced putative kinase 1), DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1), LRRK-2 (Leucine-rich repeat kinase 2), parkin and α-synuclein (SNCA), are associated with mitochondria or are mitochondrial proteins. ![]() All of the proteins associated with familial forms of PD are involved in the pathways of oxidative stress and free radical damage. The identification of mutations in a few specific genes involved in PD indicates the relevance of both mitochondrial dysfunction and oxidative stress in the sporadic and familial forms of the disease. Moreover, the pathological role of mitochondrial respiratory chain dysfunction and also the roles of oxidative stress in neurodegenerative disease such as AD and PD are well known. Oxidative stress conditions may also make T-cells resistant to growth or death stimulators. The important intracellular signaling molecules in RA are reactive oxygen species (ROS), which may damage matrix components and enhance the synovial inflammatory proliferative response in immune system cells. Indeed, diseases such as rheumatoid arthritis (RA), Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), cardiovascular disease, allergies, immune system dysfunctions, diabetes, and cancer are all related to oxidative stress. The important relationship between oxidative stress and a wide variety of human diseases has placed this stress factor at the forefront of diseases research. The perceptual origin of “oxidative stress” is tracked back to the 1950s and the term began to be used frequently by scientists from 1970 as they started to unravel the effects of free radicals and ionizing radiation. The term oxidative stress is commonly used to describe an imbalance between the systemic manifestation of free radicals and the capability of cells to detoxify them and negate their damaging effects on proteins, lipids, and DNA. 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. Although they share the targets in reversing the cytotoxic effects of H 2O 2, they seem to have distinct mechanism of function. 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). 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 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. Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. ![]() 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). 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. 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.
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