Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrPres accumulation. To evaluate the effect of curcumin on amyloid fibrillation of prion protein, we first investigated the effect of curcumin on mouse prion protein (mPrP) in a cell-free system. Curcumin reduced the prion fibril formation significantly. Furthermore, we monitored the change in apoptosis and reactive oxygen species (ROS) level upon curcumin treatment in mouse neuroblastoma cells (N2a). Curcumin effectively rescues the cells from apoptosis and decreases the ROS level caused by subsequent co-incubation with prion amyloid fibrils. The assays in cell-free mPrP and in N2a cells of this work verified the promising effect of curcumin on the prevention of transmissible neurodegenerative diseases.

Antibiotic resistance has become a crisis. Candida tropicalis (C. tropicalis) is one of the most highly virulent and drug-resistant pathogens. An alternative antimicrobial therapy to eradicate C. tropicalis effectively, without the risk of developing drug-resistance, is needed. Photodynamic therapy (PDT) is an alternative therapy that does not carry the risk of undesired drug resistance. To target the pathogens and to enhance the cellular penetration of the applied photosensitizer, we fabricated cationic chitosan/tripolyphosphate nanoparticles to encapsulate phthalocyanine. Our strategy promotes the uptake of phthalocyanine four-fold. This enhanced PDT can effectively inhibit planktonic C. tropicalis, such that only ~20% of C. tropicalis in the test survived; but it has a limited ability to inhibit adherent C. tropicalis. Further tests with adherent C. tropicalis indicated that sequential treatment with PDT and flucytosine significantly eliminates pseudohyphae and yeast-like C. tropicalis cells. The cell viability is only ~10% after this sequential treatment. This study provides evidence of an effective therapy against drug resistant C. tropicalis, and this strategy can be potentially applied to other pathogens.

Prion diseases or transmissible spongiform encephalopathies are a rare group of fatal neurodegenerative illnesses in humans and animals caused by misfolding of prion protein (PrP). Prion protein is a cell-surface glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed mostly in the central and peripheral nervous system, and this membrane-bound protein can be cleaved from the cell membranes by phosphoinositide phospholipase C. Numerous studies have investigated GPI-free recombinant PrP, but the role of GPI on misfolding of PrP is not well known. In this study, we synthesized a GPI analog that was covalently linking to a PrP S230C mutant, resulting in S230C-GPI. The structural changes in S230C-GPI upon binding to lipid vesicles composed of mixtures of the zwitterionic lipid (POPC) and the anionic lipid (POPG) were analyzed by circular dichroism spectroscopy, and the amyloid aggregation of S230C-GPI in the liberation from phospholipid vesicles was monitored by proteinase K-digestion assay. Our results indicate that S230C-GPI in the liberation of lipid vesicles has high tendency to misfold into amyloid fibrils, while the membrane-bound S230C-GPI proteins are highly stable and rarely convert into amyloid forms. In addition, the role of cholesterol in S230C-GPI was studied. The effect of GPI, cholesterol and phospholipid vesicles on misfolding of PrP is further discussed.

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The representative structures of the denatured state ensemble of ubiquitin under a native condition and heat-denatured ubiquitin simulated from a fully extended conformation.