title: 4-Hydroxy-2-nonenal, a reactive product of lipid peroxidation, and neurodegenerative diseases: a toxic combination illuminated by redox proteomics studies.
abstract: CONCLUSIONS
  Among different forms of oxidative stress, lipid peroxidation comprises the interaction of free radicals with polyunsaturated fatty acids, which in turn leads to the formation of highly reactive electrophilic aldehydes. Among these, the most abundant aldehydes are 4-hydroxy-2-nonenal (HNE) and malondialdehyde, while acrolein is the most reactive. HNE is considered a robust marker of oxidative stress and a toxic compound for several cell types. Proteins are particularly susceptible to modification caused by HNE, and adduct formation plays a critical role in multiple cellular processes.
  
  
  BACKGROUND
  With the outstanding progress of proteomics, the identification of putative biomarkers for neurodegenerative disorders has been the main focus of several studies and will continue to be a difficult task.
  
  
  RESULTS
  The present review focuses on the role of lipid peroxidation, particularly of HNE-induced protein modification, in neurodegenerative diseases. By comparing results obtained in different neurodegenerative diseases, it may be possible to identify both similarities and specific differences in addition to better characterize selective neurodegenerative phenomena associated with protein dysfunction. Results obtained in our laboratory and others support the common deregulation of energy metabolism and mitochondrial function in neurodegeneration.
  
  
  CONCLUSIONS
  Research towards a better understanding of the molecular mechanisms involved in neurodegeneration together with identification of specific targets of oxidative damage is urgently required. Redox proteomics will contribute to broaden the knowledge in regard to potential biomarkers for disease diagnosis and may also provide insight into damaged metabolic networks and potential targets for modulation of disease progression.
authors: Department of Biochemical Sciences, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy. marzia.perluigi@uniroma1.it
authors: Marzia
authors: M
authors: Perluigi
authors: Raffaella
authors: R
authors: Coccia
authors: D Allan
authors: DA
authors: Butterfield
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008315:Malondialdehyde; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D011506:Proteins; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal