Mitochondria as an Easy Target to Oxidative Stress Events in Parkinson's Disease

Author(s): Marcella Reale, Mirko Pesce, Medha Priyadarshini, Mohammad A Kamal, Antonia Patruno.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 11 , Issue 4 , 2012

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Abstract:

Parkinson’s disease (PD) is related to excess production of reactive oxygen species (ROS) or inadequate and impaired detoxification by endogenous antioxidants, alterations in catecholamine metabolism, alterations in mitochondrial electron transfer function, and enhanced iron deposition in the substantia nigra. The concept that oxidative stress is an important mechanism underlying the degeneration of dopaminergic (DAergic) neurons is reinforced by data documenting that high levels of lipid peroxidation, increased oxidation of proteins and DNA and depletion of glutathione are observed in postmortem studies of brain tissues of PD patients. Tyrosine hydroxylase (TH) is an important neuronal enzyme that, in the presence of tetrahydrobiopterin, catalyzes the initial and rate-limiting step in the biosynthesis of the catecholamine neurotransmitters dopamine (DA) and norepinephrine, and is frequently used as a marker of DAergic neuronal loss in animal models of PD. The role for TH as generators of ROS are highly relevant to PD because ROS have been proposed to contribute to the neurodegeneration of DA neurons. Oxidants and superoxide radicals are produced as byproducts of oxidative phosphorylation, making mitochondria the main site of ROS generation within the cell and the site of the first line of defence against oxidative stress. ROS can affect mitochondrial DNA (mtDNA) causing modulation in synthesis of electron transport chain (ETC) components, decreased ATP production, and increased leakage of ROS.

Keywords: Parkinson's disease, oxidative stress, mitochondria, tyrosine hydroxylase.

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Article Details

VOLUME: 11
ISSUE: 4
Year: 2012
Page: [430 - 438]
Pages: 9
DOI: 10.2174/187152712800792875
Price: $58

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