Effective Reduction of Tau Amyloid Aggregates in the Presence of Cyclophilin from Platanus orientalis Pollens; An Alternative Mechanism of Action of the Allergen.

BACKGROUND: A hallmark pathology of Alzheimer's disease (AD) is the construction of neurofibrillary tangles, which are made of hyperphosphorylated Tau. The cis-proline isomer of the pThr/Ser-Pro sequence has been suggested to act as an aggregation precursor according to the 'Cistauosis' hypothesis; however, this aggregation scheme is not yet completely approved. Various peptidyl-prolyl isomerases (PPIases) may specifically isomerize cis/trans-proline bonds and restitute Tau's ability to attach microtubules and may control Tau amyloid aggregation in AD. METHODS: In this study, we provided experimental evidence for indicating the effects of the plant Cyclophilin (P-Cyp) from Platanus orientalis pollens on the Tau aggregation by various spectroscopic techniques. RESULTS: Our findings disclosed that the rate/extent of amyloid formation in the Tau sample which is incubated with P-Cyp decreased and these observations do not seem to be due to the macromolecular crowding effect. Also, as proven that 80% of the prolines in the unfolded protein are in the trans conformation, urea-induced unfolding analyses confirmed this conclusion and showed that the aggregation rate/extent of urea-treated Tau samples decreased compared with those of the native protein. Also, XRD analysis indicated the reduction of scattering intensities and beta structures of amyloid fibrils in the presence of P-Cyp. Therefore, the ability of P-Cyp to suppress Tau aggregation probably depends on cis to trans isomerization of proline peptide bonds (X-Pro) and decreasing cis isomers in vitro. CONCLUSION: The findings of the current study may inspire possible protective/detrimental effects of various types of cyclophilins on AD onset/progression through direct regulation of intracellular Tau molecules and provides evidence that a protein from a plant source is able to enter the cell cytoplasm and may affect the behavior of cytoplasmic proteins.

Effective suppression of the modified PHF6 peptide/1N4R Tau amyloid aggregation by intact curcumin, not its degradation products: Another evidence for the pigment as preventive/therapeutic "functional food".

Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. In present study, the influence of curcumin and its degradation products (DPs) on the amyloid aggregation of Tau protein and the related PHF6 peptide were investigated. We provided experimental/theoretical evidence for suppressing effects of the compounds on the amyloid formation using far-UV CD as well as AFM, XRD and docking techniques and showed that the parent curcumin displayed stronger inhibition effect against Tau fibril aggregation. The obtained results suggest that the curcumin/DPs binding sites on the Tau molecule are likely to be the same, and provide a good structural basis to explain the efficient aggregation suppressing behavior of the curcumin, compared to the DPs. So, developing more stable curcumin nanoparticle formulations with improved curcumin bioavailability are of great importance. Curcumin's multi-functionality is also highly significant for the therapeutic application of this natural compound against various human diseases.

Antiradical activity of different parts of Walnut (Juglans regia L.) fruit as a function of genotype.

The objective of this work was to analyse phenolic compounds and antiradical capacity of different parts of walnut fruit among six genotypes of Juglans regia L. Therefore, total phenolic and flavonoid content were determined and methanolic extracts of walnut genotypes were considered by the reducing power, DPPH (2,2-diphenyl-1-picrylhydrazyl), superoxide anion and nitric oxide radical scavenging. Significant differences were found in phenolic content and radical scavenging capacity of different parts of fruits and among various genotypes. High correlation coefficient (R(2)=0.81) was observed between phenol content and radical scavenging activity, but this was not always true (R(2)=0.01). These results demonstrated that walnut genotypes have different phenolic compounds and phenolic compounds have different radical scavenging power. The differences of phenolic compounds were confirmed by using high performance liquid chromatography (HPLC).