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Few-layer bismuth selenides exfoliated by hemin inhibit amyloid-β1-42 fibril formation.

Peng J, Xiong Y, Lin Z, Sun L, Weng J - Sci Rep (2015)

Bottom Line: The results show that smaller and thinner few-layer Bi(2)Se(3) had the highest inhibition efficiency.The results indicate that the inhibition effect may be due to the high adsorption capacity of few-layer Bi(2)Se(3) for Aβ(1-42) monomers.Few-layer Bi(2)Se(3) also decreased Aβ-mediated peroxidase-like activity and cytotoxicity according to in vitro neurotoxicity studies under physiological conditions.

View Article: PubMed Central - PubMed

Affiliation: 1] College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P.R. China [2] College of Materials, Xiamen University, Xiamen 361005, P.R. China.

ABSTRACT
Inhibiting amyloid-β (Aβ) fibril formation is the primary therapeutic strategy for Alzheimer's disease. Several small molecules and nanomaterials have been used to inhibit Aβ fibril formation. However, insufficient inhibition efficiency or poor metabolization limits their further applications. Here, we used hemin to exfoliate few-layer Bi(2)Se(3) in aqueous solution. Then we separated few-layer Bi(2)Se(3) with different sizes and thicknesses by fractional centrifugation, and used them to attempt to inhibit Aβ(1-42) aggregation. The results show that smaller and thinner few-layer Bi(2)Se(3) had the highest inhibition efficiency. We further investigated the interaction between few-layer Bi(2)Se(3) and Aβ(1-42) monomers. The results indicate that the inhibition effect may be due to the high adsorption capacity of few-layer Bi(2)Se(3) for Aβ(1-42) monomers. Few-layer Bi(2)Se(3) also decreased Aβ-mediated peroxidase-like activity and cytotoxicity according to in vitro neurotoxicity studies under physiological conditions. Therefore, our work shows the potential for applications of few-layer Bi(2)Se(3) in the biomedical field.

No MeSH data available.


Related in: MedlinePlus

Inhibiting Aβ1-42 fibril formation by few-layer Bi2Se3 with different thicknesses investigating by ThT assay.Kinetics of Aβ1-42 fibril formation at 37°C in presence of few-layer Bi2Se3 with thickness of 10 ± 8 nm (mixture, a) , 15 ± 3 nm (b), 6 ± 2 nm (c), 3 ± 1 nm (d) and hemin (e). (f) ThT fluorescence intensity of Aβ1-42 monomer, Aβ1-42 fibril, Aβ1-42 incubated at 37°C for 3 h in presence of hemin and few-layer Bi2Se3 with different thicknesses, respectively. Fluorescence emissions were monitored at 485 nm with excitation at 442 nm. Three replicates were performed.
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f3: Inhibiting Aβ1-42 fibril formation by few-layer Bi2Se3 with different thicknesses investigating by ThT assay.Kinetics of Aβ1-42 fibril formation at 37°C in presence of few-layer Bi2Se3 with thickness of 10 ± 8 nm (mixture, a) , 15 ± 3 nm (b), 6 ± 2 nm (c), 3 ± 1 nm (d) and hemin (e). (f) ThT fluorescence intensity of Aβ1-42 monomer, Aβ1-42 fibril, Aβ1-42 incubated at 37°C for 3 h in presence of hemin and few-layer Bi2Se3 with different thicknesses, respectively. Fluorescence emissions were monitored at 485 nm with excitation at 442 nm. Three replicates were performed.

Mentions: Thioflavine T (ThT) is a classic amyloid dye that is frequently used to probe Aβ fibril formation due to its strong fluorescence emission upon binding to cross-β fibril structures474849. We co-incubated Aβ1-42 monomer and few-layer Bi2Se3 with different concentrations, and then monitored Aβ fibril formation kinetics by ThT fluorescence assay. Modified Krebs-Henseliet buffer, which mimics near-physiological conditions8, was used in the following experiments except where specifically noted. Aβ1-42 fibril formation in modified Krebs-Henseliet buffer without few-layer Bi2Se3 was firstly investigated by ThT fluorescence assay (Supplementary Fig. S10). In the absence of few-layer Bi2Se3, Aβ1-42 formed ThT-positive β-sheets instantaneously and ThT fluorescence reached maximum intensity at 3 h and then decreased gradually. Therefore, 3 h was selected as the appropriate time to study the effect of few-layer Bi2Se3 on Aβ1-42 fibril formation. The Aβ fibril formation kinetics in the absence and presence of few-layer Bi2Se3 with different thicknesses are shown in Fig. 3. Before fractional centrifugation, few-layer Bi2Se3 with a wide thickness distribution (10 ± 8 nm) was named a mixture. When the mixture was introduced (Fig. 3a), the fluorescence intensity at 3 h gradually decreased with increasing concentration of few-layer Bi2Se3, indicating consistent inhibition of Aβ1-42 fibril formation by few-layer Bi2Se3 in a dose-dependent manner. To further investigate the effect of few-layer Bi2Se3 thickness on Aβ1-42 fibril formation, few-layer Bi2Se3 with different thicknesses were introduced (Fig. 3b-d). Similarly, fluorescence intensities at 3 h gradually decreased with increasing concentration of few-layer Bi2Se3. It is interesting that the fluorescence intensity at 3 h gradually decreased with decreasing thickness of few-layer Bi2Se3 at a same concentration, indicating the inhibition efficiency increased with decreasing layers of few-layer Bi2Se3 (Table 1 and Fig. 3f). Few-layer Bi2Se3 contains 11.8% hemin calculated by TGA and XPS data (Supplementary Fig. S8). In order to investigate the effect of hemin on Aβ1-42 fibril formation, the corresponding hemin in few-layer Bi2Se3 with different concentrations was calculated and incubated with Aβ1-42 monomer in similar conditions (Fig. 3e and Table 1). Compared with few-layer Bi2Se3, the decrease of ThT fluorescence intensity induced by hemin was negligible. Therefore, the high inhibition efficiency of few-layer Bi2Se3 resulted mainly from few-layer Bi2Se3 (Fig. 3f, Table 1). Finally, the end-point ThT intensities at 3 h versus different Aβ inhibitors were plotted (Fig. 3f) and few-layer Bi2Se3 of 3 ± 1 nm had the best efficiency in inhibiting Aβ fibril formation. Therefore, few-layer Bi2Se3 of 3 ± 1 nm was used in following experiments except where specifically noted.


Few-layer bismuth selenides exfoliated by hemin inhibit amyloid-β1-42 fibril formation.

Peng J, Xiong Y, Lin Z, Sun L, Weng J - Sci Rep (2015)

Inhibiting Aβ1-42 fibril formation by few-layer Bi2Se3 with different thicknesses investigating by ThT assay.Kinetics of Aβ1-42 fibril formation at 37°C in presence of few-layer Bi2Se3 with thickness of 10 ± 8 nm (mixture, a) , 15 ± 3 nm (b), 6 ± 2 nm (c), 3 ± 1 nm (d) and hemin (e). (f) ThT fluorescence intensity of Aβ1-42 monomer, Aβ1-42 fibril, Aβ1-42 incubated at 37°C for 3 h in presence of hemin and few-layer Bi2Se3 with different thicknesses, respectively. Fluorescence emissions were monitored at 485 nm with excitation at 442 nm. Three replicates were performed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4446900&req=5

f3: Inhibiting Aβ1-42 fibril formation by few-layer Bi2Se3 with different thicknesses investigating by ThT assay.Kinetics of Aβ1-42 fibril formation at 37°C in presence of few-layer Bi2Se3 with thickness of 10 ± 8 nm (mixture, a) , 15 ± 3 nm (b), 6 ± 2 nm (c), 3 ± 1 nm (d) and hemin (e). (f) ThT fluorescence intensity of Aβ1-42 monomer, Aβ1-42 fibril, Aβ1-42 incubated at 37°C for 3 h in presence of hemin and few-layer Bi2Se3 with different thicknesses, respectively. Fluorescence emissions were monitored at 485 nm with excitation at 442 nm. Three replicates were performed.
Mentions: Thioflavine T (ThT) is a classic amyloid dye that is frequently used to probe Aβ fibril formation due to its strong fluorescence emission upon binding to cross-β fibril structures474849. We co-incubated Aβ1-42 monomer and few-layer Bi2Se3 with different concentrations, and then monitored Aβ fibril formation kinetics by ThT fluorescence assay. Modified Krebs-Henseliet buffer, which mimics near-physiological conditions8, was used in the following experiments except where specifically noted. Aβ1-42 fibril formation in modified Krebs-Henseliet buffer without few-layer Bi2Se3 was firstly investigated by ThT fluorescence assay (Supplementary Fig. S10). In the absence of few-layer Bi2Se3, Aβ1-42 formed ThT-positive β-sheets instantaneously and ThT fluorescence reached maximum intensity at 3 h and then decreased gradually. Therefore, 3 h was selected as the appropriate time to study the effect of few-layer Bi2Se3 on Aβ1-42 fibril formation. The Aβ fibril formation kinetics in the absence and presence of few-layer Bi2Se3 with different thicknesses are shown in Fig. 3. Before fractional centrifugation, few-layer Bi2Se3 with a wide thickness distribution (10 ± 8 nm) was named a mixture. When the mixture was introduced (Fig. 3a), the fluorescence intensity at 3 h gradually decreased with increasing concentration of few-layer Bi2Se3, indicating consistent inhibition of Aβ1-42 fibril formation by few-layer Bi2Se3 in a dose-dependent manner. To further investigate the effect of few-layer Bi2Se3 thickness on Aβ1-42 fibril formation, few-layer Bi2Se3 with different thicknesses were introduced (Fig. 3b-d). Similarly, fluorescence intensities at 3 h gradually decreased with increasing concentration of few-layer Bi2Se3. It is interesting that the fluorescence intensity at 3 h gradually decreased with decreasing thickness of few-layer Bi2Se3 at a same concentration, indicating the inhibition efficiency increased with decreasing layers of few-layer Bi2Se3 (Table 1 and Fig. 3f). Few-layer Bi2Se3 contains 11.8% hemin calculated by TGA and XPS data (Supplementary Fig. S8). In order to investigate the effect of hemin on Aβ1-42 fibril formation, the corresponding hemin in few-layer Bi2Se3 with different concentrations was calculated and incubated with Aβ1-42 monomer in similar conditions (Fig. 3e and Table 1). Compared with few-layer Bi2Se3, the decrease of ThT fluorescence intensity induced by hemin was negligible. Therefore, the high inhibition efficiency of few-layer Bi2Se3 resulted mainly from few-layer Bi2Se3 (Fig. 3f, Table 1). Finally, the end-point ThT intensities at 3 h versus different Aβ inhibitors were plotted (Fig. 3f) and few-layer Bi2Se3 of 3 ± 1 nm had the best efficiency in inhibiting Aβ fibril formation. Therefore, few-layer Bi2Se3 of 3 ± 1 nm was used in following experiments except where specifically noted.

Bottom Line: The results show that smaller and thinner few-layer Bi(2)Se(3) had the highest inhibition efficiency.The results indicate that the inhibition effect may be due to the high adsorption capacity of few-layer Bi(2)Se(3) for Aβ(1-42) monomers.Few-layer Bi(2)Se(3) also decreased Aβ-mediated peroxidase-like activity and cytotoxicity according to in vitro neurotoxicity studies under physiological conditions.

View Article: PubMed Central - PubMed

Affiliation: 1] College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P.R. China [2] College of Materials, Xiamen University, Xiamen 361005, P.R. China.

ABSTRACT
Inhibiting amyloid-β (Aβ) fibril formation is the primary therapeutic strategy for Alzheimer's disease. Several small molecules and nanomaterials have been used to inhibit Aβ fibril formation. However, insufficient inhibition efficiency or poor metabolization limits their further applications. Here, we used hemin to exfoliate few-layer Bi(2)Se(3) in aqueous solution. Then we separated few-layer Bi(2)Se(3) with different sizes and thicknesses by fractional centrifugation, and used them to attempt to inhibit Aβ(1-42) aggregation. The results show that smaller and thinner few-layer Bi(2)Se(3) had the highest inhibition efficiency. We further investigated the interaction between few-layer Bi(2)Se(3) and Aβ(1-42) monomers. The results indicate that the inhibition effect may be due to the high adsorption capacity of few-layer Bi(2)Se(3) for Aβ(1-42) monomers. Few-layer Bi(2)Se(3) also decreased Aβ-mediated peroxidase-like activity and cytotoxicity according to in vitro neurotoxicity studies under physiological conditions. Therefore, our work shows the potential for applications of few-layer Bi(2)Se(3) in the biomedical field.

No MeSH data available.


Related in: MedlinePlus