A particular subgroup of protein-misfolding diseases, comprising Alzheimer's and Parkinson's disease, involves amyloidogenic proteins that can form alternative pathogenic conformations with a high tendency to self-assemble into oligomeric and fibrillar species. Although misfolded proteins have been clearly linked to disease, the exact nature of the toxic species remains highly controversial. Increasing evidence suggests that there is little correlation between the occurrence of macroscopic protein deposits and toxic phenotypes in affected cells and tissues. In this article, we recap amyloid aggregation pathways, describe prion-like propagation, elaborate on detrimental interactions of protein aggregates with the cellular protein quality control system and discuss why some aggregates are toxic, whereas others seem to be beneficial. On the basis of recent studies on prion strains, we reason that the specific aggregate conformation and the resulting individual interaction with the cellular environment might be the major determinant of toxicity.
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October 2016
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Patricija van Oosten-Hawle
Patricija van Oosten-Hawle
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A schematic depiction of protease network in mitochondria. In this issue, Voos et al. review mitochondrial protein quality control, looking at the biochemical processes and the enzymatic components that are responsible for maintaining mitochondrial protein homeostasis; see pages 213–225. - PDF Icon PDF LinkTable of Contents
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Review Article|
October 15 2016
Shape matters: the complex relationship between aggregation and toxicity in protein-misfolding diseases
Heidrun Maja Ries;
Heidrun Maja Ries
1Center for Molecular Biology of Heidelberg University (ZMBH) and German Cancer Research Center (DKFZ), DKFZ–ZMBH Alliance, Heidelberg 69120, Germany
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Carmen Nussbaum-Krammer
Carmen Nussbaum-Krammer
*
1Center for Molecular Biology of Heidelberg University (ZMBH) and German Cancer Research Center (DKFZ), DKFZ–ZMBH Alliance, Heidelberg 69120, Germany
*Correspondence: Carmen Nussbaum-Krammer (email c.nussbaum@zmbh.uni-heidelberg.de).
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Publisher: Portland Press Ltd
Received:
January 14 2016
Revision Received:
April 18 2016
Accepted:
April 29 2016
Online ISSN: 1744-1358
Print ISSN: 0071-1365
© 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2016
Essays Biochem (2016) 60 (2): 181–190.
Article history
Received:
January 14 2016
Revision Received:
April 18 2016
Accepted:
April 29 2016
Citation
Patricija van Oosten-Hawle, Heidrun Maja Ries, Carmen Nussbaum-Krammer; Shape matters: the complex relationship between aggregation and toxicity in protein-misfolding diseases. Essays Biochem 15 October 2016; 60 (2): 181–190. doi: https://doi.org/10.1042/EBC20160008
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