Metals, oxidative stress and neurodegenerative disorders
- PMID: 20730621
- DOI: 10.1007/s11010-010-0563-x
Metals, oxidative stress and neurodegenerative disorders
Abstract
The neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD), are age-related disorders characterized by the deposition of abnormal forms of specific proteins in the brain. AD is characterized by the presence of extracellular amyloid plaques and intraneuronal neurofibrillary tangles in the brain. Biochemical analysis of amyloid plaques revealed that the main constituent is fibrillar aggregates of a 39-42 residue peptide referred to as the amyloid-β protein (Aβ). PD is associated with the degeneration of dopaminergic neurons in the substantia nigra pars compacta. One of the pathological hallmarks of PD is the presence of intracellular inclusions called Lewy bodies that consist of aggregates of the presynaptic soluble protein called α-synuclein. There are various factors influencing the pathological depositions, and in general, the cause of neuronal death in neurological disorders appears to be multifactorial. However, it is clear, that the underlying factor in the neurological disorders is increased oxidative stress substantiated by the findings that the protein side-chains are modified either directly by reactive oxygen species (ROS) or reactive nitrogen species (RNS), or indirectly, by the products of lipid peroxidation. The increased level of oxidative stress in AD brain is reflected by the increased brain content of iron (Fe) and copper (Cu) both capable of stimulating free radical formation (e.g. hydroxyl radicals via Fenton reaction), increased protein and DNA oxidation in the AD brain, enhanced lipid peroxidation, decreased level of cytochrome c oxidase and advanced glycation end products (AGEs), carbonyls, malondialdehyde (MDA), peroxynitrite, and heme oxygenase-1 (HO-1). AGEs, mainly through their interaction with receptors for advanced glycation end products (RAGEs), further activate signaling pathways, inducing formation of proinflammatory cytokines such as interleukin-6 (IL-6). The conjugated aromatic ring of tyrosine residues is a target for free-radical attack, and accumulation of dityrosine and 3-nitrotyrosine has also been reported in AD brain. The oxidative stress linked with PD is supported by both postmortem studies and by studies showing the increased level of oxidative stress in the substantia nigra pars compacta, demonstrating thus the capacity of oxidative stress to induce nigral cell degeneration. Markers of lipid peroxidation include 4-hydroxy-trans-2-nonenal (HNE), 4-oxo-trans-2-nonenal (4-ONE), acrolein, and 4-oxo-trans-2-hexenal, all of which are well recognized neurotoxic agents. In addition, other important factors, involving inflammation, toxic action of nitric oxide (NO·), defects in protein clearance, and mitochondrial dysfunction all contribute to the etiology of PD. It has been suggested that several individual antioxidants or their combinations can be neuroprotective and decrease the risk of AD or slow its progression. The aim of this review is to discuss the role of redox metals Fe and Cu and non-redox metal zinc (Zn) in oxidative stress-related etiology of AD and PD. Attention is focused on the metal-induced formation of free radicals and the protective role of antioxidants [glutathione (GSH), vitamin C (ascorbic acid)], vitamin E (α-Tocopherol), lipoic acid, flavonoids [catechins, epigallocatechin gallate (EGCG)], and curcumin. An alternate hypothesis topic in AD is also discussed.
Similar articles
-
Detection and localization of markers of oxidative stress by in situ methods: application in the study of Alzheimer disease.Methods Mol Biol. 2010;610:419-34. doi: 10.1007/978-1-60327-029-8_25. Methods Mol Biol. 2010. PMID: 20013193 Free PMC article.
-
The redox chemistry of the Alzheimer's disease amyloid beta peptide.Biochim Biophys Acta. 2007 Aug;1768(8):1976-90. doi: 10.1016/j.bbamem.2007.02.002. Epub 2007 Feb 9. Biochim Biophys Acta. 2007. PMID: 17433250 Review.
-
Therapeutic potentials of plant iridoids in Alzheimer's and Parkinson's diseases: A review.Eur J Med Chem. 2019 May 1;169:185-199. doi: 10.1016/j.ejmech.2019.03.009. Epub 2019 Mar 8. Eur J Med Chem. 2019. PMID: 30877973 Review.
-
Advances in metal-induced oxidative stress and human disease.Toxicology. 2011 May 10;283(2-3):65-87. doi: 10.1016/j.tox.2011.03.001. Epub 2011 Mar 23. Toxicology. 2011. PMID: 21414382 Review.
-
Metals, toxicity and oxidative stress.Curr Med Chem. 2005;12(10):1161-208. doi: 10.2174/0929867053764635. Curr Med Chem. 2005. PMID: 15892631 Review.
Cited by
-
Oxidant/Antioxidant imbalance and the risk of Alzheimer's disease.Curr Alzheimer Res. 2015;12(4):335-49. doi: 10.2174/1567205012666150325182702. Curr Alzheimer Res. 2015. PMID: 25817254 Free PMC article. Review.
-
Assessment of Protective Role of Multifunctional Dopamine Agonist D-512 Against Oxidative Stress Produced by Depletion of Glutathione in PC12 Cells: Implication in Neuroprotective Therapy for Parkinson's Disease.Neurotox Res. 2015 Nov;28(4):302-18. doi: 10.1007/s12640-015-9548-6. Epub 2015 Jul 23. Neurotox Res. 2015. PMID: 26201265 Free PMC article.
-
Preventing expression of the nicotinic receptor subunit α7 in SH-SY5Y cells with interference RNA indicates that this receptor may protect against the neurotoxicity of Aβ.Neurochem Res. 2013 May;38(5):943-50. doi: 10.1007/s11064-013-1001-8. Epub 2013 Feb 21. Neurochem Res. 2013. PMID: 23430468
-
Multiple-Ascending-Dose Pharmacokinetics and Safety Evaluation of Baicalein Chewable Tablets in Healthy Chinese Volunteers.Clin Drug Investig. 2016 Sep;36(9):713-724. doi: 10.1007/s40261-016-0418-7. Clin Drug Investig. 2016. PMID: 27352310 Clinical Trial.
-
Nanoprobing of the effect of Cu(2+) cations on misfolding, interaction and aggregation of amyloid β peptide.J Neuroimmune Pharmacol. 2013 Mar;8(1):262-73. doi: 10.1007/s11481-012-9416-6. Epub 2012 Nov 11. J Neuroimmune Pharmacol. 2013. PMID: 23143330 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous