Detection of Oxidatively-Modified Proteins in Human Cerebrospinal Fluid (CSF) Using an Aldehyde Reactive Probe

摘要

Oxidative stress and inflammation are believed to be critically involved in the pathogenesis of many neurodegenerative disorders such as Alzheimer's disease (AD) (Varadarajan et al., 2000). Protein carbonyls, a marker of protein oxidation, are known to be increased in AD brain, indicating that oxidative modification of proteins is relevant in AD. Free radical mediated injury is prevented or attenuated by intrinsic antioxidant systems. In diseased regions of AD brain, redox imbalance leads to elevated levels of lipid peroxidation (LPO) and reactive species from LPO, such as 4-hydroxy-2-nonenal (HNE) (Butterfield et al., 2002). Cerebrospinal fluid (CSF) is derived in part from brain interstitial fluid and, therefore, is proximate to the degenerating tissue. As an initial effort to develop biomarkers for the early detection of AD, we employed a targeted proteomics approach for the identification of oxidatively-modified proteins in CSF.