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Protein misfolding, aggregation, and degradation in disease

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Abstract

Pathologies associated with protein misfolding have been observed in neurodegenerative diseases such as Alzheimer’s disease, metabolic diseases like phenylketonuria, and diseases affecting structural proteins like collagen or keratin. Misfolding of mutant proteins in these and many other diseases may result in premature degradation, formation of toxic aggregates, or incorporation of toxic conformations into structures. We review common traits of these diverse diseases under the unifying view of protein misfolding. The molecular pathogenesis is discussed in the context of protein quality control systems consisting of molecular chaperones and intracellular proteases that assist the folding and supervise the maintenance of the folded structure. Furthermore, genetic and environmental factors that may modify the severity of these diseases are underscored.

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Authors and Affiliations

  1. Research Unit for Molecular Medicine, Institute for Clinical Medicine, Aarhus University Hospital SKS, Brendstrupgaardsvej, 8200, Århus N, Denmark

    Niels Gregersen & Peter Bross

  2. Department of Human Genetics, Aarhus University Hospital SKS, Brendstrupgaardsvej, 8200, Århus N, Denmark

    Lars Bolund

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  1. Niels Gregersen
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  2. Lars Bolund
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  3. Peter Bross
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Correspondence to Peter Bross.

Additional information

The present article represents a partly revised and updated version of chapter 1 published earlier in volume 232 of the series Methods in Molecular Biology (Walker, J. M., ed., Humana Press, Totowa, NJ), Protein Misfolding and Disease: Principles and Protocols (Bross, P. & Gregersen, N., eds.), pp. 3–16 (2003).

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Gregersen, N., Bolund, L. & Bross, P. Protein misfolding, aggregation, and degradation in disease. Mol Biotechnol 31, 141–150 (2005). https://doi.org/10.1385/MB:31:2:141

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