Solubilization of β-amyloid-(1-42)-peptide

Reversing the β-sheet conformation induced by aluminum with silicates

G. D. Fasman, A. Perczel, C. D. Moore

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Plaques are one of the two lesions found in the brain of patients with Alzheimer disease. Using a synthetic peptide corresponding to rat β-amyloid- (1-42) (βA4), circular dichroism (CD) analyses were performed to examine the effect of Na4SiO4 on the conformational state produced by Al3+. A previous study on fragments of neuronal proteins involved in tangle formation had shown a conformational transition from a β-pleated sheet to a soluble random coil upon addition of Na4SiO4. In the present study, CD measurements showed that the β-pleated sheet conformation of βA4 induced by Al3+ was reversed to the random coil soluble form by the addition of Na4SiO4. The tight binding of SiO4/4- with Al3+ provides the mechanism for this transition. These results provide insight into the role of aluminum in the Alzheimer diseased brain and suggests the investigation of the use of silicates as a therapeutic agent.

Original languageEnglish
Pages (from-to)369-371
Number of pages3
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number2
DOIs
Publication statusPublished - 1995

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Aluminum Silicates
Circular Dichroism
Amyloid
Alzheimer Disease
Silicates
Peptides
Brain
Aluminum
Proteins
Therapeutics

Keywords

  • circular dichroism
  • conformational changes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "Solubilization of β-amyloid-(1-42)-peptide: Reversing the β-sheet conformation induced by aluminum with silicates",
abstract = "Plaques are one of the two lesions found in the brain of patients with Alzheimer disease. Using a synthetic peptide corresponding to rat β-amyloid- (1-42) (βA4), circular dichroism (CD) analyses were performed to examine the effect of Na4SiO4 on the conformational state produced by Al3+. A previous study on fragments of neuronal proteins involved in tangle formation had shown a conformational transition from a β-pleated sheet to a soluble random coil upon addition of Na4SiO4. In the present study, CD measurements showed that the β-pleated sheet conformation of βA4 induced by Al3+ was reversed to the random coil soluble form by the addition of Na4SiO4. The tight binding of SiO4/4- with Al3+ provides the mechanism for this transition. These results provide insight into the role of aluminum in the Alzheimer diseased brain and suggests the investigation of the use of silicates as a therapeutic agent.",
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T1 - Solubilization of β-amyloid-(1-42)-peptide

T2 - Reversing the β-sheet conformation induced by aluminum with silicates

AU - Fasman, G. D.

AU - Perczel, A.

AU - Moore, C. D.

PY - 1995

Y1 - 1995

N2 - Plaques are one of the two lesions found in the brain of patients with Alzheimer disease. Using a synthetic peptide corresponding to rat β-amyloid- (1-42) (βA4), circular dichroism (CD) analyses were performed to examine the effect of Na4SiO4 on the conformational state produced by Al3+. A previous study on fragments of neuronal proteins involved in tangle formation had shown a conformational transition from a β-pleated sheet to a soluble random coil upon addition of Na4SiO4. In the present study, CD measurements showed that the β-pleated sheet conformation of βA4 induced by Al3+ was reversed to the random coil soluble form by the addition of Na4SiO4. The tight binding of SiO4/4- with Al3+ provides the mechanism for this transition. These results provide insight into the role of aluminum in the Alzheimer diseased brain and suggests the investigation of the use of silicates as a therapeutic agent.

AB - Plaques are one of the two lesions found in the brain of patients with Alzheimer disease. Using a synthetic peptide corresponding to rat β-amyloid- (1-42) (βA4), circular dichroism (CD) analyses were performed to examine the effect of Na4SiO4 on the conformational state produced by Al3+. A previous study on fragments of neuronal proteins involved in tangle formation had shown a conformational transition from a β-pleated sheet to a soluble random coil upon addition of Na4SiO4. In the present study, CD measurements showed that the β-pleated sheet conformation of βA4 induced by Al3+ was reversed to the random coil soluble form by the addition of Na4SiO4. The tight binding of SiO4/4- with Al3+ provides the mechanism for this transition. These results provide insight into the role of aluminum in the Alzheimer diseased brain and suggests the investigation of the use of silicates as a therapeutic agent.

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