The presence of amyloid fibers in mature neutrophils / 实用医学杂志

Objective To investigate whether there is amyloid fibers in the mature neutrophils and to reveal the molecular mechanism of the formation of AD amyloidosis. Method Thirty cases of AD patients and 30 healthy control were enrolled. The white blood cell, the red blood cell,hemoglobin and neutrophil absolute value were determined by Sysmex X5-500i hematology analyzer. The neutrophils and amyloid variable specific probe affinity were measured, The starch like variable fluorescence intensity in plasma was dtected by the sulfur T (Thioflavin T, ThT) method. Results The affinity test results showed that the amyloidosis fluorescent probe (ThT) can be combined with tissue amyloid fibers specifically. The neutrophil amyloid fibers staining also showed a positive reaction. Compared with the AD group, no significant differences were found in white blood cell, red blood cell, hemoglobin and neutrophil absolute value level in the healthy control group The serum amyloid variable fluorescence intensity in the AD group was significantly higher than that in the control group (P < 0.05). Conclusion The amyloid fibers was found in the mature neutrophils, and the level of plasma amyloid fibers was significantly increased in the AD patients.

Effect of clioquinol on aggregation ofβ-amyloid in vitro / 国际药学研究杂志

Objective To study whether the metal chelator clioquinol (CQ) can affectβ-amyloid (Aβ) aggregation directly in vitro and whether this effect could be influenced by Zn2+. Methods In the study thioflavin T (Th-T) fluorescence was used to detect the aggregated Aβ. To eliminate the possible false positive results, the absorption spectrum (300 nm to 600 nm) of CQ was scanned, and a competitive binding assay was applied to determine whether Th-T and CQ had the same binding site on Aβ. Circular dichroism spectroscopy was used to detect β-sheet formation of Aβ. Results CQ could decrease the fluorescence intensity, when incubated with monomer Aβor aggregated Aβfor 24 h. Absorption spectra indicated that CQ had no specific absorption peak at 450 nm and 485 nm. Competitive binding assay showed that CQ and Th-T did not bind the same site on Aβ. CD spectra showed that CQ could decrease theβ-sheet formation of Aβ. When incubated with monomer Aβ, CQ decreased the fluorescence intensity in a dose dependent manner, and the IC50 were 6.1μmol/L (without Zn2+) and 4.3μmol/L (with Zn2+);When incubated with aggregated Aβ, CQ decreased the fluorescence intensity in a dose dependent mannerand, and the IC50 was 7.5μmol/L (without Zn2+) and 6.1μmol/L (with Zn2+). Conclusion CQ can inhibit the aggregation of monomer Aβand depolymerize the aggregated Aβdirectly in vitro. Zn2+has little influence on the effect of CQ on Aβ.

Phytomedicines as potential inhibitors of β amyloid aggregation: significance to Alzheimer's disease / 中国天然药物

Throughout the history of drug development, plants have been an important source for the discovery of novel therapeutically active compounds for many diseases. The ethnopharmacological approach has provided several leads to identify potential new drugs from plant sources, including those for memory disorders. For the treatment of Alzheimer's disease the drug discovery focus shifted from cholinesterase inhibitors, to other targets primarily based on two key neuropathological hallmarks, namely the hyperphosphorylation of the tau protein resulting in the formation of neurofibrillary tangles (NFTs), and the increased formation and aggregation of amyloid-beta peptide (Aβ) derived from amyloid precursor protein (APP). The present article aims to provide a comprehensive literature survey of plants and their constituents that have been tested for Aβ aggregation, thus possibly relieving several features of Alzheimer's disease (AD).

Effect of clioquinol on aggregation of β-amyloid in vitro / 国际药学研究杂志

Objective To study whether the metal chelator clioquinol (CQ) can affect β-amyloid (Aβ) aggregation directly in vitro and whether this effect could be influenced by Zn2c. Methods In the study thioflavin T (Th-T) fluorescence was used to detect the aggregated Aβ. To eliminate the possible false positive results, the absorption spectrum (300 nm to 600 nm) of CQ was scanned, and a competitive binding assay was applied to determine whether Th-T and CQ had the same binding site on Aβ. Circular dichroism spectroscopy was used to detect β-sheet formation of Aβ. Results CQ could decrease the fluorescence intensity, when incubated with monomer Aβ or aggregated Aβ for 24 h. Absorption spectra indicated that CQ had no specific absorption peak at 450 nm and 485 nm. Competitive binding assay showed that CQ and Th-T did not bind the same site on Aβ. CD spectra showed that CQ could decrease the β-sheet formation of Aβ. When incubated with monomer Aβ, CQ decreased the fluorescence intensity in a dose dependent manner, and the IC50 were 6.1 "mol/L (without Zn2c) and 4.3 "mol/L (with Zn2c); When incubated with aggregated Aβ, CQ decreased the fluorescence intensity in a dose dependent mannerand, and the IC50 was 7.5 "mol/L (without Zn2c) and 6.1 "mol/L (with Zn2c). Conclusion CQ can inhibit the aggregation of monomer Aβ and depolymerize the aggregated Aβ directly in vitro. Zn2c has little influence on the effect of CQ on Aβ.