Roles of 3-nitrotyrosine- and 4-hydroxynonenal-modified brain proteins in the progression and pathogenesis of Alzheimer's disease

Abstract

Proteins play an important role in normal structure and function of the cells. Oxidative modification of proteins may greatly alter the structure and may subsequently lead to loss of normal physiological cell functions and may lead to abnormal function of cell and eventually to cell death. These modifications may be reversible or irreversible. Reversible protein modifications, such as phosphorylation, can be overcome by specific enzymes that cause a protein to ‘revert’ back to its original protein structure, while irreversible protein modifications cannot. Several important irreversible protein modifications include protein nitration and HNE modification, both which have been extensively investigated in research on the progression of Alzheimer's disease (AD). From the earliest stage of AD throughout the advancement of the disorder there is evidence of increased protein nitration and HNE modification. These protein modifications lead to decreased enzymatic activity, which correlates directly to protein efficacy and provides support for several common themes in AD pathology, namely altered energy metabolism, mitochondrial dysfunction and reduced cholinergic neurotransmission. The current review summarized some of the findings on protein oxidation related to different stages of Alzheimer's disease (AD) that will be helpful in understanding the role of protein oxidation in the progression and pathogenesis of AD.

Keywords::

• Alzheimer's disease
• mild cognitive impairment
• early Alzheimer's disease
• protein nitration
• lipid peroxidation
• 4-hydroxy 2-trans nonenal
• proteomics

This paper was first published online on Early Online on 4 October 2010.