Dai C, Whitesell L, Rogers AB, Lindquist S.
Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis.
Cell. 2007 Sep 21;130(6):1005-18.
PubMed.
One provocative question of this paper is, What is the impact of altering HSF-1 activity in the CNS? This is of particular interest to the field because inhibitors of Hsp90 (inducers of the heat shock response) are beginning to emerge as a viable therapeutic approach to treat neurodegenerative disorders associated with abnormal protein accumulation. Molecular chaperones may protect against these diseases by promoting the formation of less toxic protein aggregates and/or by targeting toxic, misfolded proteins for degradation through the ubiquitin-proteasome system. Will ramping up the heat shock response in the CNS increase the risk for cancer and/or deregulate the cell cycle in postmitotic cells? Intriguing data from both the cancer and neuroscience fields suggests that Hsp90 inhibitors may act selectively in pathological cells, sparing normal cells. Yet how altered HSF-1 activity varies in peripheral tissue compared with the central nervous system is unknown.
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Mayo Clinic College of Medicine
One provocative question of this paper is, What is the impact of altering HSF-1 activity in the CNS? This is of particular interest to the field because inhibitors of Hsp90 (inducers of the heat shock response) are beginning to emerge as a viable therapeutic approach to treat neurodegenerative disorders associated with abnormal protein accumulation. Molecular chaperones may protect against these diseases by promoting the formation of less toxic protein aggregates and/or by targeting toxic, misfolded proteins for degradation through the ubiquitin-proteasome system. Will ramping up the heat shock response in the CNS increase the risk for cancer and/or deregulate the cell cycle in postmitotic cells? Intriguing data from both the cancer and neuroscience fields suggests that Hsp90 inhibitors may act selectively in pathological cells, sparing normal cells. Yet how altered HSF-1 activity varies in peripheral tissue compared with the central nervous system is unknown.
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