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Inhibition of Beta-Amyloid Fibrillation by Luminescent Iridium(III) Complex Probes.

Lu L, Zhong HJ, Wang M, Ho SL, Li HW, Leung CH, Ma DL - Sci Rep (2015)

Bottom Line: We report herein the application of kinetically inert luminescent iridium(III) complexes as dual inhibitors and probes of beta-amyloid fibrillogenesis.These iridium(III) complexes inhibited Aβ1-40 peptide aggregation in vitro, and protected against Aβ-induced cytotoxicity in neuronal cells.Furthermore, the complexes differentiated between the aggregated and unaggregated forms of Aβ1-40 peptide on the basis of their emission response.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.

ABSTRACT
We report herein the application of kinetically inert luminescent iridium(III) complexes as dual inhibitors and probes of beta-amyloid fibrillogenesis. These iridium(III) complexes inhibited Aβ1-40 peptide aggregation in vitro, and protected against Aβ-induced cytotoxicity in neuronal cells. Furthermore, the complexes differentiated between the aggregated and unaggregated forms of Aβ1-40 peptide on the basis of their emission response.

No MeSH data available.


Related in: MedlinePlus

Neuroprotective effect of 14 against Aβ1–40 peptide-induced cytotoxicity towards (a–d) human neuroblastoma SH-SY5Y cells and (e–h) mouse primary cortical cells.Cell viability is expressed as a percentage of control cells exposed to 0.5% DMSO. The histograms show the cell viability of various concentrations of Aβ1–40 peptide monomer (M), Aβ1–40 peptide with seeded fibril (MS), and fibrillar Aβ1–40 peptide (F), in the presence of 14. Various forms of Aβ1–40 peptide were incubated for (a,b,e,f) 2 h, and for (c,d,g,h) 24 h at [Aβ1–40]:[14] ratios of 0.2:1, 1:1, and 5:1.
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f5: Neuroprotective effect of 14 against Aβ1–40 peptide-induced cytotoxicity towards (a–d) human neuroblastoma SH-SY5Y cells and (e–h) mouse primary cortical cells.Cell viability is expressed as a percentage of control cells exposed to 0.5% DMSO. The histograms show the cell viability of various concentrations of Aβ1–40 peptide monomer (M), Aβ1–40 peptide with seeded fibril (MS), and fibrillar Aβ1–40 peptide (F), in the presence of 14. Various forms of Aβ1–40 peptide were incubated for (a,b,e,f) 2 h, and for (c,d,g,h) 24 h at [Aβ1–40]:[14] ratios of 0.2:1, 1:1, and 5:1.

Mentions: The effect of 14 on Aβ1–40-induced cytotoxicity in SH-SY5Y cells and mouse primary cortical cells was also investigated. The cytotoxicity of three different forms of Aβ1–40 peptide in the presence and the absence of 14 were examined: Aβ1–40 peptide monomer (M), Aβ1–40 peptide monomer with seeded fibrils (MS) and Aβ1–40 fibril (F) (Fig. 5). The results showed that treatment of cells with different forms of Aβ1–40 peptides caused toxicity to SH-SY5Y cells and mouse primary cortical cells (Fig. 4a,c,e,g). Encouragingly, 14 exhibited a neuroprotective effect against the cytotoxicity induced by all three forms of Aβ1–40 peptide at [Aβ1–40]/[14] ratios of 0.2, 1.0, or 5.0 for SH-SY5Y cells (Fig. 5a,b) or mouse primary cortical cells (Fig. 5e,f) after 2 h of incubation. The neuroprotective effects of 14 were still observable after 24 h of incubation of 14 (Fig. 5c,d,g,h). As a negative control, we also investigated the effect of 12, which showed no effect against amyloid aggregation, on Aβ1–40-induced toxicity. The results showed that 12 had no neuroprotective effect against cytotoxicity induced by all three forms of Aβ1–40 peptide at [Aβ1–40]/[12] ratios of 0.2, 1.0, or 5.0 in SH-SY5Y cells (Figure S6). Taken together, these data indicate that 14 displays neuroprotective effects against Aβ-mediated cytotoxicity when administered at a low enough dosage in SH-SY5Y cells and mouse primary cortical cells.


Inhibition of Beta-Amyloid Fibrillation by Luminescent Iridium(III) Complex Probes.

Lu L, Zhong HJ, Wang M, Ho SL, Li HW, Leung CH, Ma DL - Sci Rep (2015)

Neuroprotective effect of 14 against Aβ1–40 peptide-induced cytotoxicity towards (a–d) human neuroblastoma SH-SY5Y cells and (e–h) mouse primary cortical cells.Cell viability is expressed as a percentage of control cells exposed to 0.5% DMSO. The histograms show the cell viability of various concentrations of Aβ1–40 peptide monomer (M), Aβ1–40 peptide with seeded fibril (MS), and fibrillar Aβ1–40 peptide (F), in the presence of 14. Various forms of Aβ1–40 peptide were incubated for (a,b,e,f) 2 h, and for (c,d,g,h) 24 h at [Aβ1–40]:[14] ratios of 0.2:1, 1:1, and 5:1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588514&req=5

f5: Neuroprotective effect of 14 against Aβ1–40 peptide-induced cytotoxicity towards (a–d) human neuroblastoma SH-SY5Y cells and (e–h) mouse primary cortical cells.Cell viability is expressed as a percentage of control cells exposed to 0.5% DMSO. The histograms show the cell viability of various concentrations of Aβ1–40 peptide monomer (M), Aβ1–40 peptide with seeded fibril (MS), and fibrillar Aβ1–40 peptide (F), in the presence of 14. Various forms of Aβ1–40 peptide were incubated for (a,b,e,f) 2 h, and for (c,d,g,h) 24 h at [Aβ1–40]:[14] ratios of 0.2:1, 1:1, and 5:1.
Mentions: The effect of 14 on Aβ1–40-induced cytotoxicity in SH-SY5Y cells and mouse primary cortical cells was also investigated. The cytotoxicity of three different forms of Aβ1–40 peptide in the presence and the absence of 14 were examined: Aβ1–40 peptide monomer (M), Aβ1–40 peptide monomer with seeded fibrils (MS) and Aβ1–40 fibril (F) (Fig. 5). The results showed that treatment of cells with different forms of Aβ1–40 peptides caused toxicity to SH-SY5Y cells and mouse primary cortical cells (Fig. 4a,c,e,g). Encouragingly, 14 exhibited a neuroprotective effect against the cytotoxicity induced by all three forms of Aβ1–40 peptide at [Aβ1–40]/[14] ratios of 0.2, 1.0, or 5.0 for SH-SY5Y cells (Fig. 5a,b) or mouse primary cortical cells (Fig. 5e,f) after 2 h of incubation. The neuroprotective effects of 14 were still observable after 24 h of incubation of 14 (Fig. 5c,d,g,h). As a negative control, we also investigated the effect of 12, which showed no effect against amyloid aggregation, on Aβ1–40-induced toxicity. The results showed that 12 had no neuroprotective effect against cytotoxicity induced by all three forms of Aβ1–40 peptide at [Aβ1–40]/[12] ratios of 0.2, 1.0, or 5.0 in SH-SY5Y cells (Figure S6). Taken together, these data indicate that 14 displays neuroprotective effects against Aβ-mediated cytotoxicity when administered at a low enough dosage in SH-SY5Y cells and mouse primary cortical cells.

Bottom Line: We report herein the application of kinetically inert luminescent iridium(III) complexes as dual inhibitors and probes of beta-amyloid fibrillogenesis.These iridium(III) complexes inhibited Aβ1-40 peptide aggregation in vitro, and protected against Aβ-induced cytotoxicity in neuronal cells.Furthermore, the complexes differentiated between the aggregated and unaggregated forms of Aβ1-40 peptide on the basis of their emission response.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.

ABSTRACT
We report herein the application of kinetically inert luminescent iridium(III) complexes as dual inhibitors and probes of beta-amyloid fibrillogenesis. These iridium(III) complexes inhibited Aβ1-40 peptide aggregation in vitro, and protected against Aβ-induced cytotoxicity in neuronal cells. Furthermore, the complexes differentiated between the aggregated and unaggregated forms of Aβ1-40 peptide on the basis of their emission response.

No MeSH data available.


Related in: MedlinePlus