期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 1, 期 1, 页码 52-57出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2004.11.004
关键词
Huntington's disease; Nanofibrils; Atomic force microscopy
资金
- Hereditary Disease Foundation
Background: Huntington's disease is an autosomal dominant progressive neurodegenerative disease associated with dramatic expansion of a polyglutamine sequence in exon 1 of the huntingtin protein htt that leads to cytoplasmic, and even nuclear aggregation of fibrils. Methods: We have studied the in vitro fibril formation of mutant exon 1, and the shorter wild-type exon 1, with use of atomic force microscopy (AFM). Results: Large aggregates are formed spontaneously after cleavage of the glutathione-S-transferase fusion protein of the mutant exon 1 protein. The AFM data showed that, unlike fibrils assembled by such proteins as amyloid beta-peptide and alpha-synuclein, htt forms fibrils with extensive branched morphologic features. Branching can be observed even at earlier stages of the htt self-assembly, but the effect is much more pronounced at late stages of aggregation. We also found that fusing of htt with green fluorescent protein does not change the branched-type morphologic features of the aggregates. Conclusions: On the basis of the results obtained, we propose a model for htt fibrillization that explains branched morphologic features of the aggregates. (C) 2005 Elsevier Inc. All rights reserved.
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