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Molecular Pathways to Polyglutamine Aggregation

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Tandem Repeat Polymorphisms

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB))

Abstract

Over 100 human cellular proteins contain a repetitive polyglutamine tract, however, only nine of these proteins are associated with disease. In these proteins, the expanded polyQ tract perturbs the native conformation, resulting in an ordered aggregation process that leads to the formation of amyloid-like fibrils. The misfolding pathway involves the formation of prefibrillar oligomeric structures, which are proposed to be involved in cellular toxicity. Non-polyQ host protein regions modulate the misfolding pathway, suggesting an importance of protein context in aggregation. This chapter describes the current research regarding polyQ misfolding, with emphasis on the species populated during aggregation, suggesting an important role of protein context in modulating the aggregation pathway.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

    Amy L. Robertson & Stephen P. Bottomley

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  1. Amy L. Robertson
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  2. Stephen P. Bottomley
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Correspondence to Stephen P. Bottomley .

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  1. Florey Neuroscience Institutes, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria, Australia

    Anthony J. Hannan Phd

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Robertson, A.L., Bottomley, S.P. (2012). Molecular Pathways to Polyglutamine Aggregation. In: Hannan, A.J. (eds) Tandem Repeat Polymorphisms. Advances in Experimental Medicine and Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5434-2_7

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