doi:10.1016/j.bbrc.2005.11.053 
Copyright © 2005 Elsevier Inc. All rights reserved.
Influence of heparin and dendrimers on the aggregation of two amyloid peptides related to Alzheimer’s and prion diseases
Barbara Klajnerta, Marta Cortijo-Arellanob, Maria Bryszewskaa and Josep Claderab, 
, 
aDepartment of General Biophysics, University of Lodz, ul. Banacha 12/16, Lodz 90-237, Poland
bBiophysics Unit, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain
Received 7 November 2005.
Available online 17 November 2005.
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Abstract
Amyloid plaques composed of proteinaceous aggregates are commonly found in brains affected by Alzheimer’s disease and spongiform encephalopaties. A structural homology has been recently described for the Alzheimer’s peptide Aβ1–28 and the segment of the prion protein Prp185–208. In the present paper, further elements in common are reported: the aggregation processes are in both cases enhanced by the model glucosaminoglycan heparin and dendrimers can modulate the aggregation process by affecting the nucleation rate at low concentrations and the elongation rate at high concentrations. Nucleation and elongation rate constants are derived from fittings to a nucleation dependent polymerization model.
Keywords: Amyloid; Alzheimer; Prion; Dendrimer; Heparin
Fig. 1. Structure of a generation three (G3) PAMAM dendrimer.
Fig. 2. Thioflavin T fluorescence variation during the aggregation processes of the amyloidogenic peptides in 10 mM Tris buffer, pH 5.5. (A) Aβ1–28 (•); Aβ1–28 in the presence of heparin 0.041 mg/ml (■); Aβ1–28 in the presence of 5 μM PAMAM-G3 (
). (B) Prp185–208 (■); Prp185–208 in the presence of heparin 0.041 mg/ml (•). Peptide concentration was 50 μM. Temperature was set at 37 °C. The samples were continuously stirred during fluorescence measurements. ThT concentration was 35 μM.
Fig. 3. Thioflavin T fluorescence variation during the aggregation processes of the amyloidogenic peptides in 10 mM Tris buffer, pH 5.5, and 0.041 mg/ml heparin, as a function of dendrimer PAMAM-G3 concentration. (A) Aβ1-28: 0.001(), 0 (control) (•), 0.1 (○), 1 (■), and 5 (
) μM PAMAM-G3. (B) Prp185-208: 0.01 (
), 0 (control) (•), 0.15 (○), 0.25 (), and 1 (■) μM PAMAM-G3. Experimental conditions were set as in Fig. 1.
Fig. 4. Kinetic analysis of Aβ1–28 aggregation in the presence of heparin. The continuous line corresponds to the mathematical fit of the ThT fluorescence variation of 50 μM Aβ1–28 in 10 mM Tris buffer and 0.041 mg/ml heparin, pH 5.5 (data from Fig. 2A), to Eq. (1). Prior to the fitting, data were transformed into fractions of total fibril formation. The nucleation and elongation constants derived from the fitting are given in Table 1.
Table 1.
Nucleation and elongation rate constants calculated by fitting experimental data in Fig. 2 to Eq. (1)
The parameters ρ and k, derived from Eq. (1) have been used to calculate the rate constants: kn = ρk and ke=k/a (a = initial peptide concentration). Rate constants units are given according to [27].
Abstract
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