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The interplay between the chaperonin TRiC and N-terminal region of Huntingtin mediates Huntington’s Disease aggregation and pathogenesis

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Protein Quality Control in Neurodegenerative Diseases

Part of the book series: Research and Perspectives in Alzheimer's Disease ((ALZHEIMER))

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Abstract

Huntington’s Disease (HD) is a neurodegenerative disorder resulting from an expanded polyglutamine (polyQ) repeat in exon1 of the Huntingtin (Htt) protein. This polyQ expansion causes aggregation of the Htt protein in neuronal cells, which is linked to HD pathogenesis. Recent evidence has shown that Htt aggregation and toxicity are not solely dictated by the polyQ-expanded region but also by sequences flanking the polyQ region, particularly the first N-terminal 17 amino acids of Htt (N17). N17 has been shown to be critical in the Htt aggregation mechanism as well as host many post-translational modifications and interactions with molecular chaperones. Understanding how N17 functions in Htt aggregation and as a general handle for protein quality control will guide design of HD therapeutics.

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  1. Department of Biology and BioX Program, Stanford University, Stanford, CA, 94305-5020, USA

    Koning Shen & Judith Frydman

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  1. Koning Shen
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  2. Judith Frydman
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Correspondence to Judith Frydman .

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  1. Morimoto Lab, Northwestern University, 2205 Tech Drive, Evanston, 60208-3500, Illinois, USA

    Richard I. Morimoto

  2. Fondation IPSEN, Quai Georges Gorse 65, Boulogne-Billancourt Cedex, 92650, France

    Yves Christen

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Shen, K., Frydman, J. (2013). The interplay between the chaperonin TRiC and N-terminal region of Huntingtin mediates Huntington’s Disease aggregation and pathogenesis. In: Morimoto, R., Christen, Y. (eds) Protein Quality Control in Neurodegenerative Diseases. Research and Perspectives in Alzheimer's Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27928-7_10

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