期刊
PROTEOMICS CLINICAL APPLICATIONS
卷 3, 期 6, 页码 636-653出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/prca.200800195
关键词
Biomarkers; Cellular stress response; Diagnostics; Neurodegeneration; Oncoproteomics
The HSP family is one of the most ancient and evolutionarily conserved protective protein families found in nature. Originally discovered as inducible molecules capable of maintaining cellular homeostasis against abrupt temperature changes, HSPs were later determined to represent an adaptive physiological response that copes with a variety of different cellular proteotoxic stresses. These physiological molecular chaperones facilitate the synthesis, folding, assembly, trafficking and secretion of specific proteins in various cellular compartments. Most importantly, these proteins guard the whole cell proteome against misfolding and inappropriate aggregation. A series of diversified proteotoxic stresses, including heat, hypoxia/ischemia, free radicals, acidosis, ATP depletion and toxins are capable of inducing a typical cellular stress response characterised by rapid inhibition of overall protein synthesis, with a concomitant dramatic increase in H S P expression. From a pathophsiological point of view, HSP induction has been observed in a wide spectrum of inflammatory and degenerative diseases (from cancer to prion disease by passing to infective and autoimmune diseases) and, intriguingly, overexpression monitoring seems to have potential implications in terms of diagnosis, prognosis and, above all, therapy. Proteomics studies, identifying a series of modification of HSP expression patterns in different diseases, are confirming these promising clinical applications.
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