Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo

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Item Type:	Article
Title:	Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo
Creators Name:	Scherzinger, E., Lurz, R., Turmaine, M., Mangiarini, L., Hollenbach, B., Hasenbank, R., Bates, G.P., Davies, S.W., Lehrach, H. and Wanker, E.E.
Abstract:	The mechanism by which an elongated polyglutamine sequence causes neurodegeneration in Huntington's disease (HD) is unknown. In this study, we show that the proteolytic cleavage of a GST-huntingtin fusion protein leads to the formation of insoluble high molecular weight protein aggregates only when the polyglutamine expansion is in the pathogenic range. Electron micrographs of these aggregates revealed a fibrillar or ribbon-like morphology, reminiscent of scrapie prions and beta-amyloid fibrils in Alzheimer's disease. Subcellular fractionation and ultrastructural techniques showed the in vivo presence of these structures in the brains of mice transgenic for the HD mutation. Our in vitro model will aid in an eventual understanding of the molecular pathology of HD and the development of preventative strategies.
Keywords:	Amino Acid Sequence, Amyloid, Base Sequence, Brain, Cell Nucleus, DNA Primers, Exons, Glutathione Transferase, Huntington Disease, Kidney, Macromolecular Substances, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Proteins, Polymerase Chain Reaction, Recombinant Fusion Proteins, Animals, Mice
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	90
Number:	3
Page Range:	549-558
Date:	8 August 1997
Official Publication:	https://doi.org/10.1016/S0092-8674(00)80514-0
PubMed:	View item in PubMed

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