NDLI: Isolating Toxic Insulin Amyloid Reactive Species that Lack β-Sheets and Have Wide pH Stability

Content Provider	PubMed Central
Author	Heldt, Caryn L. Dmitry, Kurouski Sorci, Mirco Elizabeth, Grafeld Lednev, Igor K. Belfort, Georges
Copyright Year	2011
Abstract	Amyloid diseases, including Alzheimer's disease, are characterized by aggregation of normally functioning proteins or peptides into ordered, β-sheet rich fibrils. Most of the theories on amyloid toxicity focus on the nuclei or oligomers in the fibril formation process. The nuclei and oligomers are transient species, making their full characterization difficult. We have isolated toxic protein species that act like an oligomer and may provide the first evidence of a stable reactive species created by disaggregation of amyloid fibrils. This reactive species was isolated by dissolving amyloid fibrils at high pH and it has a mass >100 kDa and a diameter of 48 ± 15 nm. It seeds the formation of fibrils in a dose dependent manner, but using circular dichroism and deep ultraviolet resonance Raman spectroscopy, the reactive species was found to not have a β-sheet rich structure. We hypothesize that the reactive species does not decompose at high pH and maintains its structure in solution. The remaining disaggregated insulin, excluding the toxic reactive species that elongated the fibrils, returned to native structured insulin. This is the first time, to our knowledge, that a stable reactive species of an amyloid reaction has been separated and characterized by disaggregation of amyloid fibrils.
Related Links	http://dx.doi.org/10.1016/j.bpj.2011.04.046
Ending Page	2800
Page Count	9
Starting Page	2792
File Format	PDF
ISSN	00063495
e-ISSN	15420086
Journal	Biophysical Journal
Issue Number	11
Volume Number	100
Language	English
Publisher	The Biophysical Society
Publisher Date	2011-06-01
Access Restriction	Open
Rights Holder	The Biophysical Society
Subject Keyword	Biophysics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biophysics

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