Application of proteomics technologies in the investigation of the brain

Abstract I. Introduction 232 II. Proteomic Analysis 233 A. Sample Preparation 233 B. Two‐Dimensional (2‐D) Electrophoresis 234 C. Protein Quantification 235 D. Mass Spectrometry (MS) 236 1. Matrix‐Assisted Laser Desorption/Ionization Time‐of‐Flight Mass Spectroscopy (MALDI‐TOF‐MS) 236 2. Tandem MS 237 III. 2‐D Brain Protein Databases 238 A. Database Construction 238 B. Subcellular Location 240 C. Frequency of Detection 240 D. Protein Function 242 IV. Alterations in the Protein Levels 243 A. Adult Brain 243 B. Fetal Brain 245 V. Proteomic Studies on Rat Brain 245 A. Differences Between Neonatal and Adult Brain 245 B. Post‐Mortem Changes 248 C. Toxicology Studies 248 VI. Limitations 248 A. Brain Samples 248 B. Protein Detection in 2‐D Gels 249 1. Low‐Abundance Proteins 249 2. Hydrophobic Proteins 250 3. Acidic and Basic Proteins 251 4. Low‐ and High‐Molecular Mass Proteins 251 5. Protein Heterogeneity 251 C. Protein Indentification 252 VII. Perspectives 253 VIII. Conclusions 253 Acknowledgments 254 References 254 Approximately 30–50% of the genes in mammals are expressed in the nervous system. A differential expression of genes in distinct patterns is necessary for the generation of the large variety of neuronal phenotypes. Proteomic analysis of brain compartments may be useful to understand the complexity, to investigate disorders of the central nervous system, and to search for corresponding early markers. Up to now, proteomics has mainly studied the identity and levels of the abundant human, rat, and mouse brain proteins as well as changes of their levels and the modifications that result from various neurological disorders, like Alzheimer's disease and Down's syndrome in humans and in animal models of those diseases. The proteins, for which altered levels in these disorders have been observed, exert mainly neurotransmission, guidance, and signal‐transduction functions, or are involved in detoxification, metabolism, and conformational changes. Some of those proteins may be potential drug targets. Further improvement of proteomics technologies to increase sensitivity and efficiency of detection of certain protein classes is necessary for a more detailed analysis of the brain proteome. In this review, a description of the proteomics technologies applied in the investigation of the brain, the major findings that resulted from their application, and the potential and limitations of the current technologies are discussed. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 23:231–258, 2004