When Alzheimer's disease (AD) progresses, several pathological features arise including accumulation of misfolded protein aggregates [e.g., amyloid-β (Aβ) plaques], metal ion dyshomeostasis, and oxidative stress. These characteristics are recently suggested to be interconnected through a potential factor, metal-associated Aβ (metal-Aβ) species. The role of metal-Aβ species in AD pathogenesis remains unclear, however. To elucidate the contribution of metal-Aβ species to AD pathology, as well as to develop small molecules as chemical tools and/or theranostic (therapeutic and diagnostic) agents for this disease, curcumin (Cur), a natural product from turmeric, and its derivatives have been studied towards both metal-free and metal-induced Aβ aggregation. Although Cur has indicated anti-amyloidogenic activities and antioxidant properties, its biological use has been hindered due to low solubility and stability in physiologically relevant conditions. Herein, we report the reactivity of Cur and its derivatives (Gd-Cur, a potential multimodal Aβ imaging agent; Cur-S, a water soluble derivative of Cur that has substitution at the phenolic hydroxyls) with metal-free Aβ and metal-Aβ species. Our results and observations indicate that Gd-Cur could modulate Cu(II)-triggered Aβ aggregation more noticeably over metal-free or Zn(II)-induced analogues; however, Cur-S was not observed to noticeably modulate Aβ aggregation with and without metal ions. Overall, our studies present information that could aid in optimizing the molecular scaffold of Cur for the development of chemical tools or theranostics for metal-Aβ species.
This review describes recent research efforts focused on increasing the specificity of contrast agents for proton magnetic resonance imaging (MRI). Contrast agents play an indispensable role in MRI by enhancing the inherent contrast of images; however, the non-specific nature of current clinical contrast agents limits their usefulness. This limitation can be addressed by conjugating contrast agents or contrast-agent-loaded carriers—including polymers, nanoparticles, dendrimers, and liposomes—to molecules that bind to biological sites of interest. An alternative approach to conjugation is synthetically mimicking biological structures with metal complexes that are also contrast agents. In this review, we describe the advantages and limitations of these two targeting strategies with respect to translation from in vitro to in vivo imaging while focusing on advances from the last ten years.
A multimodal, β-amyloid-targeted contrast agent was synthesized and studied in vitro. The agent has a higher relaxivity than a clinically approved contrast agent and interacts with β-amyloid aggregates producing changes in relaxation rate and fluorescence emission.
Abstract:The investigations on a variety of proteins present in corn zein, wheat gluten, milk whey and soya have shown that these proteins possess the ability to form films which can be used in food packaging. We, therefore, selected cowpea (Vigna unguiculata), a cereal abundantly available in Sri Lanka, to investigate its polymer film forming ability. Our studies have shown that the choice of a suitable solvent, pH of the medium and the use of a plasticizer were essential to obtain useful films. In this study polyethylene glycol and glycerol were used as plasticizers. The extracted cowpea protein and the plasticizers were dissolved in hot aqueous ethanol to obtain a viscous solution. The casting technique was used to fabricate the films. A series of films were made by varying the pH from 8 to 11. For each pH a series of films was prepared by varying the concentration of polyethylene glycol from 2.5 to 10% (w/v). The fabricated films were tested for transparency, glass transition temperature, tensile strength and water vapour permeability. The pH of the medium and the concentration of the plasticizer were found to have a considerable effect on the physico-chemical properties of the film. The film fabricated at pH 10 with 2.5% (w/v) of polyethylene glycol and 2% glycerol was found to possess the desired tensile strength, water vapour permeability, transparency and glass transition temperature, making the film suitable to be used as an edible food packaging material.
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