Molecular Chaperones in Health and Disease (Handbook of Experimental Pharmacology (172))

Annotation Molecular chaperones are involved in a wide variety of essential cellular processes in living cells. A subset of molecular chaperones have been initially described as heat shock proteins protecting cells from stress damage by keeping cellular proteins in a folding competent state and preventing them from irreversible aggregation. Later it became obvious that molecular chaperones are also expressed constitutively in the cell and are involved in complex processes such as protein synthesis, intracellular protein transport, post-translational modification and secretion of proteins as well as receptor signalling. Hence, it is not surprising that molecular chaperones are implicated in the pathogenesis of many relevant diseases and could be regarded as potential pharmacological targets. Starting with the analysis of the mode of action of chaperones at the molecular, cellular and organismic level, this book will then describe specific aspects where modulation of chaperone action could be of pharmacological and therapeutic interest Chaperones in Preventing Protein Denaturation in Living Cells and Protecting Against Cellular Stress....Pages 1-42 Feedback Regulation of the Heat Shock Response....Pages 43-68 Protein Folding in the Endoplasmic Reticulum and the Unfolded Protein Response....Pages 69-91 Molecular Chaperones in Signal Transduction....Pages 93-109 Chaperoning of Glucocorticoid Receptors....Pages 111-138 Heat Shock Response: Lessons from Mouse Knockouts....Pages 139-152 HSFs in Development....Pages 153-169 Heat Shock Proteins: Endogenous Modulators of Apoptotic Cell Death....Pages 171-198 Protein Aggregation as a Cause for Disease....Pages 199-219 The Role of Chaperones in Parkinson’s Disease and Prion Diseases....Pages 221-258 Chaperoning Oncogenes: Hsp90 as a Target of Geldanamycin....Pages 259-277 Heat Shock Proteins in Immunity....Pages 279-304 Molecular Chaperones and Cancer Immunotherapy....Pages 305-329 Hsp90 Inhibitors in the Clinic....Pages 331-358 Pharmacological Targeting of Catalyzed Protein Folding: The Example of Peptide Bond cis/trans Isomerases....Pages 359-404 Chemical Chaperones: Mechanisms of Action and Potential Use....Pages 405-416 Pharmacological Modulation of the Heat Shock Response....Pages 417-436