Proteomics & Disease
Proteomics is providing a better understanding of pathomechanisms of human diseases. Analysis of different levels of gene expression in healthy and diseased tissues by proteomic approaches is as important as the detection of mutations and polymorphisms at the genomic level and may be of more value in designing a rational therapy. Protein distribution / characterization in body tissues and fluids, in health as well as in disease, is the basis of the use of proteomic technologies for molecular diagnostics. Proteomics will play an important role in medicine of the future which will be personalized and will combine diagnostics with therapeutics.
Cancer
Although studies concerned with the identification of novel antigens or markers for diagnostic, prognostic, or therapeutic use have been paramount, molecules and processes implicated in carcinogenesis per se are increasingly being investigated. Most tumour markers in current use were identified from protein-based approaches, from the identification in the 1800s of an abnormal urinary precipitate in myeloma (Bence-Jones protein) to the generation of tumour-specific antibodies against epithelial cancer cell lines. Genetic markers, detected cytogenetically or by mutation detection, are also now entering clinical practice, but some changes likely to be important in carcinogenesis, diagnosis, and prognosis, such as abnormal expression of proto-oncogenes, may not be associated with a detectable genetic lesion. For proteins implicated in cancer, the use of multiple antibodies allows simultaneous characterisation of several proteins acting in a network. For example, overexpression and many post-translational modifications (largely phosphorylations) of several oncogene products and cell-cycle proteins such as p53 can be detected in transformed liver cells. Aberrant glycosylation of many proteins with a known cancer association has been described, and proteomics-based approaches are ideally placed to characterise such post-translational modifications, although much work still needs to be done to assess their clinical significance.
Heart disease
The pathogenesis of the cardiac dysfunction is still largely unknown, but a proteomics-based approach in characterising overall changes in protein expression in heart disease and heart failure may provide new insights into the cellular mechanisms involved in cardiac dysfunction, together with new diagnostic markers and therapeutic opportunities. Federated two-dimensional electrophoresis databases of human cardiac proteins have been established (www.expasy.ch/ch2d/2d-index.html), and several hundred cardiac proteins have been identified.
Infectious diseases
Identification of proteins produced by microorganisms is facilitated by the small number of genes and the completion of genome sequencing for many micro-organisms. The main aim of most studies has been the search for new diagnostic markers, candidate antigens for vaccines, and determinants of virulence. For some of the microorganisms studied, two-dimensional electrophoresis databases are available on the internet (www.expasy.ch/).
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More application fields and related aritcles:
Genomes, Proteomes, and Medicine: Opportunities in Medical Science in the 21st Century (Celera article)
Studying heart disease using the proteomic approach
Current status and perspectives of proteomics in aging research
Antibodies in diagnostics ¨C from immunoassays to protein chips
Proteomics of the nervous system
Antibacterial vaccine design using genomics and proteomics
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