Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway.

Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway. Research Abstract Details 

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Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway. Abstract Text:

Sungmun Lee,Erik J Fernandez,Theresa A Good,

beta-amyloid peptide (Abeta) is one of the main protein components of senile plaques associated with Alzheimer's disease (AD). Abeta readily aggregates to forms fibrils and other aggregated species that have been shown to be toxic in a number of studies. In particular, soluble oligomeric forms are closely related to neurotoxicity. However, the relationship between neurotoxicity and the size of Abeta aggregates or oligomers is still under investigation. In this article, we show that different Abeta incubation conditions in vitro can affect the rate of Abeta fibril formation, the conformation and stability of intermediates in the aggregation pathway, and toxicity of aggregated species formed. When gently agitated, Abeta aggregates faster than Abeta prepared under quiescent conditions, forming fibrils. The morphology of fibrils formed at the end of aggregation with or without agitation, as observed in electron micrographs, is somewhat different. Interestingly, intermediates or oligomers formed during Abeta aggregation differ greatly under agitated and quiescent conditions. Unfolding studies in guanidine hydrochloride indicate that fibrils formed under quiescent conditions are more stable to unfolding in detergent than aggregation associated oligomers or Abeta fibrils formed with agitation. In addition, Abeta fibrils formed under quiescent conditions were less toxic to differentiated SH-SY5Y cells than the Abeta aggregation associated oligomers or fibrils formed with agitation. These results highlight differences between Abeta aggregation intermediates formed under different conditions and provide insight into the structure and stability of toxic Abeta oligomers.

Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway. Publishing Authors By Initials

S Lee,EJ Fernandez,TA Good,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, secondary research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, secondary research

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Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Protein science : a publication of the Protein Soc

VOLUME: 16

Page Numbers: 723-32

Journal Abbreviation: Protein Sci.

ISSN: 0961-8368

DAY: 27

MONTH: 02

YEAR: 2007

Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9211750

Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway. Keywords Mesh Terms:

KEYWORDS: Protein Structure, Secondary

MESH TERMS: chemistry

Chemical & Substance for Abstract: Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway. Information

Substance Name: Amyloid beta-Protein

Registry Number: 0

Grant and Affiliation Information for Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway.

AFFILIATION: Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843-3122, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R01 NS042686

ACRONYM: NS

MEDLINETA: Protein Sci

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