Use of two-dimensional electrophoretic protein maps in studies of schizophrenia

High resolution two-dimensional electrophoresis (2DE) and silver staining have provided a technology capable of mapping large numbers of proteins from tissues and body fluids. Further identification of individual proteins that have been visualized by 2DE includes their characterization by immunodetection methods and by obtaining amino acid sequences from which antibody and synthetic oligonucleotide probes can be synthesized. As many as 3,500 individual proteins may be observed on a single electrophoretogram. This capacity to observe gene products permits the scanning of as many as 3.5 megabases of the protein coding regions of the genome for mutational events on each gel, and may also provide evidence concerning abnormal rates of protein synthesis or degradation, posttranslational modifications, and the presence of gene products of exogenous origin. The application of this technology has revealed a pair of abnormal cerebrospinal fluid (CSF) proteins (40KD) in one-third of schizophrenic patients screened. These abnormal proteins have never been observed in CSF from normal controls. However, they have been detected in some diseases of the central nervous system that may be of viral origin. Structural studies on these proteins should provide evidence of their origin, while ongoing studies of brain proteins may provide additional clues about this disease.