Hsps as Pharmacological Targets in Apoptosis Modulation for Cancer Therapy

Constitutively high Hsp expression is a property of and essential for the survival of at least some cancers. Neutralizing Hsps is therefore an attractive strategy for anticancer therapy. Accordingly, Hsp90 can be inhibited by the benzoquinone ansamycin antibiotic geldanamycin and its analog 17-AAG two drugs that are currently undergoing clinical trials for anti-cancer activity (Neckers 2002 Neckers and Ivy 2003). The fact that geldanamycin and 17-AAG selectively kills cancer cells has been...

References

Abe M, Manola JB, Oh WK, Parslow DL, George DJ, Austin CL, Kantoff PW (2004) Plasma levels of heat shock protein 70 in patients with prostate cancer a potential biomarker for prostate cancer. Clin Prostate Cancer 3 49-53 Aoyama A, Steiger RH, Frohli E, Schafer R, von Deimling A, Wiestler OD, Klemenz R (1993) Expression of alpha B-crystallin in human brain tumors. Int J Cancer 55 760-764 Bando Y, Katayama T, Kasai K, Taniguchi M, Tamatani M, Tohyama M (2003) GRP94 (94 kDa glucose-regulated...

Heat Shock Proteins and Cancer

The ability of heat shock proteins to influence the cell's fate through modulation of numerous control points, together with the fact that cells or tissues from a wide range of tumors have been shown to express unusually high levels of one or more Hsps, might endow these proteins with the unusual capacity to contribute in a decisive way and at multiple points in the process of tu-morigenesis. Experimental models support the role of Hsps in tumorigenesis since Hsp27 and Hsp70 have been shown to...

Alzheimers Disease and Tauopathies

In Alzheimer's disease, Ap peptides (Ap42 and Ap40) are the principal components of extracellular amyloid plaques. These aggregation-prone peptides are generated in the secretory pathway by the sequential action of p- and y-secretase on the transmembrane Ap precursor protein (APP) (review in Walter et al. 2001). In a cell culture model it has been shown that the ER-resident Hsp70 homolog BiP Grp78 interacts with immature APP and decreases the secretion of Ap42 and Ap40 (Yang et al. 1998)....

Formation of Inclusion Bodies Aggresomes Lewis Bodies and Russell Bodies

Cells avoid accumulating potentially toxic aggregates by mechanisms such as those discussed above, including the suppression of aggregate formation by molecular chaperones and the degradation of misfolded proteins by proteases. Once formed, aggregates tend to be refractory to proteolysis and accumulate in inclusion bodies. The term inclusion bodies has been applied to the intracellular foci into which aggregated proteins are sequestered. They are usually present in low numbers, most often only...

Determinants of Protein Aggregation

Typically, specific intermolecular interactions between hydrophobic surfaces of structural subunits in partially folded or unfolded intermediates are responsible for the formation of aggregates. An important consequence is that aggregation will be favored by factors and conditions that favor the population of these intermediates, and that aggregation will be influenced by the properties of the intermediates (Uversky 2003 Jaenicke 1995 Goldberg et al. 1991). The initial stages of aggregation are...