Redox proteomics in some age-related neurodegenerative disorders or models thereof

Abstract

Summary:Neurodegenerative diseases cause memory loss and cognitive impairment. Results from basic and clinical scientific research suggest a complex network of mechanisms involved in the process of neurodegeneration. Progress in treatment of such disorders requires researchers to better understand the functions of proteins involved in neurodegenerative diseases, to characterize their role in pathogenic disease mechanisms, and to explore their roles in the diagnosis, treatment, and prevention of neurodegenerative diseases. A variety of conditions of neurodegenerative diseases often lead to post-translational modifications of proteins, including oxidation and nitration, which might be involved in the pathogenesis of neurodegenerative diseases. Redox proteomics, a subset of proteomics, has made possible the identification of specifically oxidized proteins in neurodegenerative disorders, providing insight into a multitude of pathways that govern behavior and cognition and the response of the nervous system to injury and disease. Proteomic analyses are particularly suitable to elucidate post-translational modifications, expression levels, and protein-protein interactions of thousands of proteins at a time. Complementing the valuable information generated through the integrative knowledge of protein expression and function should enable the development of more efficient diagnostic tools and therapeutic modalities. Here we review redox proteomic studies of some neurodegenerative diseases.

Liquid chromatography with tandem mass spectrometry-based proteomic discovery in aging and Alzheimer’s disease

“…Here, basic but critically important biochemical issues come into play as protein fractions are isolated or enriched. Protein separation or isolation is typically achieved by one of three approaches: "protein chips" or activated surfaces that bind proteins based on chemical characteristics or two-dimensional (2-D) gel electrophoresis; 7,8 such methods are used in other articles in this issue including Butterfield and coworkers 4 and Choe and coworkers. 9 In contrast to these approaches, liquid chromatography (LC) also can be used to separate peptides before direct introduction to tandem mass spectrometry (MS).…”

“…In this article we will focus on a type of proteomic analysis; however, the reader is also directed to other proteomic articles in this issue. 4,5 The magnitude of the human genome and proteome is worthy of our consideration. In humans, the entire complement of protein-coding genes is now fairly solidly estimated at between 20,000 and 25,000, a surprisingly low number.…”

Herbal Antioxidants as Rejuvenators in Alternative Medicine

“…As the metabolic activity of brain is relatively high, the aberrant electron transfers result in additional free radical formation and subsequent protein nitration in aged brain tissue. Therefore, protein nitration is generally considered as a biomarker for age-related neurodegeneration (Butterfield et al, 2006;Chung and David, 2010). Moreover, nitroxidative damage of neurons can also contribute to age-related deficits in memory function.…”

Two-dimensional protein electrophoresis: From molecular pathway discovery to biomarker discovery in neurological disorders

“…50 Oxidative stress and its resultant protein, lipid, and DNA modifications are believed to play a critical role in the onset or development of age-related disorders and disease-mediated neurodegeneration. 51 Using a 2-DE carbonyl immunoblot for oxidation detection, Aksenov and coworkers 29 found increased levels of oxidation in regions of the brain that had pathophysiological changes due to AD compared with the same regions in control and in a relatively spared region of AD brain.…”