Protein Carbonylation in Neurodegenerative and Demyelinating CNS Diseases
Carbonylation is the most common protein modification that takes place as consequence of severe oxidative stress. Carbonyl (C = O) groups are introduced into proteins by direct metal-catalyzed oxidation of certain amino acids or indirectly by reaction wit
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Protein Carbonylation in Neurodegenerative and Demyelinating CNS Diseases
O. A. Bizzozero
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 544
2 2.1 2.2 2.3 2.4
Chemical and Biochemical Aspects of Protein Carbonylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545 Chemistry of Protein Carbonylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545 Measurement of Protein Carbonyls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 546 Experimental Models for Induction of Protein Carbonyls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 Removal of Protein Carbonyls from Oxidized Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549
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Functional Consequences of Protein Carbonylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 550
4 4.1 4.2 4.3 4.4 4.5 4.6 4.7
CNS Disorders Associated with Carbonylated Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 Parkinson’s Disease (PD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 552 Amyotrophic Lateral Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553 Huntington’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553 Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553 Other CNS Conditions Associated with Carbonyl Accumulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555 Protein Carbonylation Profiles in Different CNS Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555
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Pharmacological Approaches to Prevent Protein Carbonyl Formation . . . . . . . . . . . . . . . . . . . . . . . . . 555
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Concluding Remarks and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 556
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2009 Springer ScienceþBusiness Media, LLC.
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Protein carbonylation in neurodegenerative and demyelinating CNS diseases
Abstract: Carbonylation is the most common protein modification that takes place as consequence of severe
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