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A comprehensive review of the latest thinking about the molecular processes underlying conformational diseases, combined with a remarkable set of biochemical, genomic cellular, and chemical laboratory techniques for studying their genesis and pathologies. The authors apply their carefully refined methods to a variety of metabolic and neurodegenerative disorders, as well as to the aging process. The techniques presented are broadly applicable in many diverse disease contexts and may be used in both diagnosis and research on new treatment strategies.
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Methods in Molecular Biology TM VOLUME 232 Protein Misfolding and Disease Principles and Protocols Edited by Peter Bross Niels Gregersen Conformational Diseases 3 1 Protein Misfolding, Aggregation, and Degradation in Disease Niels Gregersen, Lars Bolund, and Peter Bross 1. Introduction During the last 5–10 years, it has been realized that a large number of diseases with very different pathologies at the cellular level can be discussed within a common framework of defective protein folding. Although the molecular mechanisms by which the pathologies develop are quite different, they can all be viewed as “conformational diseases.” The original concept of conformational disease was developed in relation to disorders whose hallmark was intra- or extracellular accumulation of protein aggregates, such as seen in α-1-antitrypsin deficiency with liver pathology, Alzheimer’s, Parkinson’s, and Huntington’s diseases (AD/PD/HD) (1–3). The basis for the pathology in these diseases is a cellular inability to degrade misfolded and damaged proteins and formation of cytotoxic intra- or extracellular oligomers and polymers/aggregates. The pathology in these diseases is predominantly determined by the cell damage associated with the aggregation process, thus exhib