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Mol. Cells 2013; 36(3): 185-194

Published online September 30, 2013

https://doi.org/10.1007/s10059-013-0167-x

© The Korean Society for Molecular and Cellular Biology

Aggregation Formation in the Polyglutamine Diseases: Protection at a Cost?

Tiffany W. Todd, and Janghoo Lim

1Department of Genetics, 2Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510, USA

Received: May 31, 2013; Accepted: June 2, 2013

Abstract

Mutant protein aggregation is a hallmark of many neurodegenerative diseases, including the polyglutamine disorders. Although the correlation between aggregation formation and disease pathology originally suggested that the visible inclusions seen in patient tissue might directly contribute to pathology, additional studies failed to confirm this hypothesis. Current opinion in the field of polyglutamine disease research now favors a model in which large inclusions are cytoprotective and smaller oligomers or misfolded monomers underlie pathogenesis. Nonetheless, therapies aimed at reducing or preventing aggregation show promise. This review outlines the debate about the role of aggregation in the polyglutamine diseases as it has unfolded in the literature and concludes with a brief discussion on the manipulation of aggregation formation and clearance mechanisms as a means of therapeutic intervention.

Keywords aggregation, neurodegeneration, oligomerization, polyglutamine

Article

Minireview

Mol. Cells 2013; 36(3): 185-194

Published online September 30, 2013 https://doi.org/10.1007/s10059-013-0167-x

Copyright © The Korean Society for Molecular and Cellular Biology.

Aggregation Formation in the Polyglutamine Diseases: Protection at a Cost?

Tiffany W. Todd, and Janghoo Lim

1Department of Genetics, 2Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510, USA

Received: May 31, 2013; Accepted: June 2, 2013

Abstract

Mutant protein aggregation is a hallmark of many neurodegenerative diseases, including the polyglutamine disorders. Although the correlation between aggregation formation and disease pathology originally suggested that the visible inclusions seen in patient tissue might directly contribute to pathology, additional studies failed to confirm this hypothesis. Current opinion in the field of polyglutamine disease research now favors a model in which large inclusions are cytoprotective and smaller oligomers or misfolded monomers underlie pathogenesis. Nonetheless, therapies aimed at reducing or preventing aggregation show promise. This review outlines the debate about the role of aggregation in the polyglutamine diseases as it has unfolded in the literature and concludes with a brief discussion on the manipulation of aggregation formation and clearance mechanisms as a means of therapeutic intervention.

Keywords: aggregation, neurodegeneration, oligomerization, polyglutamine

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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