Review Volume 10, Issue 5 pp 868—901

Origin and pathophysiology of protein carbonylation, nitration and chlorination in age-related brain diseases and aging

Efstathios S. Gonos1, , Marianna Kapetanou1,2, , Jolanta Sereikaite3, , Grzegorz Bartosz4, , Katarzyna Naparło5, , Michalina Grzesik5, , Izabela Sadowska-Bartosz5, ,

  • 1 National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens 11635 , Greece
  • 2 Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens 15701, Greece
  • 3 Department of Chemistry and Bioengineering, Faculty of Fundamental Sciences, Vilnius Gediminas Technical University, Vilnius 2040, Lithuania
  • 4 Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz 90-236, Poland
  • 5 Department of Analytical Biochemistry, Faculty of Biology and Agriculture, University of Rzeszow, Rzeszow 35-601, Poland

Received: April 9, 2018       Accepted: May 8, 2018       Published: May 17, 2018
How to Cite

Copyright: © 2018 Gonos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Non-enzymatic protein modifications occur inevitably in all living systems. Products of such modifications accumulate during aging of cells and organisms and may contribute to their age-related functional deterioration. This review presents the formation of irreversible protein modifications such as carbonylation, nitration and chlorination, modifications by 4-hydroxynonenal, removal of modified proteins and accumulation of these protein modifications during aging of humans and model organisms, and their enhanced accumulation in age-related brain diseases.


2D PAGE: two-dimensional polyacrylamide gel electrophoresis; 3-NT: 3-nitrotyrosine; Aβ: Amyloid beta; ACR: acrolein; AD: Alzheimer's disease; ALS: amyotrophic lateral sclerosis; AOPP: Advanced Oxidation Protein Products; DNP: dinitrophenyl; DNPH: dinitrophenylhydrazine; ECM: extracellular matrix; ESI: electro spray ionization; GC: gas chromatography; 4-HNE: 4-Hydroxy-2,3-trans-nonenal; IP: immunoprecipitation; IPL: inferior parietal lobule; MDA: malondialdehyde; MCI: mild cognitive impairment; MPO: myeloperoxidase; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MRM: Multiple Reaction Monitoring; MS: mass spectrometry; NOS: nitric oxide synthase; NS: nitr(os)ative stress; OS: oxidative stress; PD: Parkinson's disease; RCS: reactive carbonyl species; RNS: reactive nitrogen species; ROS: reactive oxygen species; RXS: reactive halogen species; SERCA: sarcoplasmic reticulum Ca2+-ATPase; SOD: superoxide dismutase; αSyn: α-synuclein; Tg: transgene; WB: Western blot; XS: halogenative stress.