Bistability of protein aggregation as a function of molecular chaperone concentration

Cells are constantly subjected to stresses; these stresses take the form of heat, heavy metals, metabolic poisons, non-native peptides, and many others. All of these stresses have the potential to cause protein misfolding, which drives protein aggregation. In neurons, long-term protein misfolding and aggregation is known to lead to the onset of neurodegenerative diseases such as Parkinson's, Huntington's, Alzheimer's, ALS, Scrapie, and others. The cellular response to stress and protein misfolding employs the mol. chaperones. In this presentation, we will explore the behavior of protein misfolding and aggregation in the presence of mol. chaperones. In line with exptl. results that show discontinuous "jumps" in aggregate concn. with subtle changes in protein concns. and cellular parameters, we demonstrate that simple models show the early stage of protein aggregation, sol. oligomer formation, is a bistable process that depends on the local concn. of mol. chaperones. Understanding the formation of the sol. oligomers is essential since many recent exptl. studies have implicated these species as the proteotoxic species in neurodegenerative disease. [on SciFinder (R)]


Published in:
Abstracts of Papers, 229th ACS National Meeting, San Diego, CA, United States, March 13-17, 2005, BIOT-326
Year:
2005
Note:
FIELD Section Title:
Department of Chemical and Biological Engineering,Northwestern University,Evanston,IL,USA. FIELD URL:
written in English.
Laboratories:




 Record created 2007-01-11, last modified 2018-03-17


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