Novel polymeric biomaterial poly(butyl-2-cyanoacrylate) nanowires: synthesis, characterization and formation mechanism.

Poly(butyl-2-cyanoacrylate) (PBCA) nanoparticles have been widely elaborated for nearly half a century. However, PBCA nanowires (PNWs) were seldom investigated. Here, new polymeric biomaterial PNWs were prepared via emulsion polymerization based on the sodium dodecyl sulfate (SDS)-assisted emulsion process. Results indicated that SDS micelles and PBCA polymer can develop surfactant-polymer complexes by self-assembly at room temperature. SDS concentration was confirmed to be the critical parameter for the association of the surfactant and the polymer. With the addition of SDS (0-40 mM), the interaction between SDS and PBCA led to a series of transitions from nanoparticles to nanowires. These morphology transitions were triggered by changing the electrostatic repulsion in the SDS-PBCA system, confirmed by the variety of zeta potential with increasing molar contents of SDS. To overcome the electrostatic repulsion, the complexes underwent transitions from spherical, worm-like (short-cylindrical), to elongated-cylindrical form. Finally, associated with the results from scanning / transmission electron microscopy (SEM / TEM), the elongated-cylindrical PNWs acquired at 20 mM of SDS were chosen to execute cell viability assay, which showed that they had no toxicity but with good-biocompatibility at the doses ≤ 50 µg/ml. These results indicate that the PNWs prepared by this facile-green and low-toxic strategy can potentially work as promising biomaterials in the biomedicine field.

A mimotope of Aß oligomers may also behave as a ß-sheet inhibitor.

Beta-amyloid (Aß) oligomers are strongly associated with the cascade of harmful events leading to neurodegeneration in Alzheimer's disease (AD). Elimination of Aß oligomers or inhibition of Aß assembly is a valuable therapeutic approach for the treatment of AD. Here, we obtained a mimotope of Aß oligomers, AOEP2, by screening a peptide library using oligomer-specific antibodies. The antibodies induced by AOEP2 specifically recognize Aß oligomers rather than monomers and fibrils. Interestingly, the AOEP2 peptide binds to Aß monomers and inhibits the formation of Aß oligomers and ß-sheet structure, reduces Aß42-induced neurotoxicity, and decreases the release of proinflammatory cytokines. Taken together, AOEP2, a novel multifunctional peptide directly or indirectly targeting Aß, has promising therapeutic potential for AD.

A vaccine with Aß oligomer-specific mimotope attenuates cognitive deficits and brain pathologies in transgenic mice with Alzheimer's disease.

BACKGROUND: ß-Amyloid peptide (Aß) oligomers are initial factors used to induce Alzheimer's disease (AD) development, and Aß monomers have normal physiological function. The antibodies or vaccines against Aß monomers have serious problems, such as side effects and low curative effects. Therefore, it is essential to specifically target Aß oligomers rather than monomers for the treatment of AD. METHODS: The mimotopes of Aß oligomers were obtained by panning the phage-displayed random peptide libraries using oligomer-specific antibodies as targets and expressed on the surface of EBY100 Saccharomyces cerevisiae to generate yeast cell base vaccines. One vaccine (AOE1) induced antibodies specifically against Aß oligomers and was selected for further study. The APP/PS1 mice were subcutaneously immunized with AOE1 eight times. The levels and characteristics of antibodies induced by AOE1 were determined by enzyme-linked immunosorbent assay. The effect of AOE1 on the cognitive deficits of AD mice was tested by novel object recognition (NOR) and Y-maze. Dot blot analysis, Western blot analysis, and immunohistochemistry were applied to measure the effects of AOE1 on Aß pathologies, neuroinflammation, and microhemorrhages in the brains of AD mice. RESULTS: Eight mimotope candidates of Aß oligomers were selected and expressed on EBY100 S. cerevisiae. Only AOE1 vaccine containing mimotope L2 induced antibodies that specifically recognized Aß42 oligomers rather than monomers. AOE1 immunization significantly increased the AD mice's exploration times for the novel object in the NOR test and the choices for new arms in the Y-maze test, and it reduced levels of Aß oligomers and glial activation in the AD mouse brains. No activation of Aß-specific T cells and microhemorrhages was observed in their brains following AOE1 vaccination. CONCLUSIONS: AOE1 is the first vaccine applying the oligomer-specific mimotope as an immunogen, which could induce antibodies with high specificity to Aß oligomers. AOE1 immunization attenuated Aß pathologies and cognitive deficits in AD mice, decreased the overactivation of glial cells, and did not induce microhemorrhage in the brains of AD mice. These findings suggest that AOE1 may be a safer and more effective vaccine for AD treatment.

Alpha-tocopherol quinine ameliorates spatial memory deficits by reducing beta-amyloid oligomers, neuroinflammation and oxidative stress in transgenic mice with Alzheimer's disease.

The pathologies of Alzheimer's disease (AD) is associated with soluble beta-amyloid (Aß) oligomers, neuroinflammation and oxidative stress. Decreasing the levels of Aß oligomer, glial activation and oxidative stress are potential therapeutic approaches for AD treatment. We previously found alpha-tocopherol quinine (α-TQ) inhibited Aß aggregation and cytotoxicity, decreased the release of inflammatory cytokines and reactive oxygen species (ROS) in vitro. However, whether α-TQ ameliorates memory deficits and other neuropathologies in mice or patients with AD remains unknown. In this study, we reported that orally administered α-TQ ameliorated memory impairment in APPswe/PS1dE9 transgenic mice, decreased oxidative stress and the levels of Aß oligomer in the brains of mice, prevented the production of inducible nitric oxide synthase and inflammatory mediators, such as interleukin-6 and interleukin-1ß, and inhibited microglial activation by inhibiting NF-κB signaling pathway. These findings suggest that α-TQ has potential therapeutic value for AD treatment.