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Many polymer-stabilized silver nanoparticles (AgNPs) with enhanced antibacterial properties have been synthesized, but very little is known about the fate of these materials and their interactions with microbes in physiological solutions. In this study, we evaluated the role of cellulose nanofibrils (CNFs) in stabilizing AgNPs (CNF-AgNPs) in a bacterial growth medi µm, determined the antibacterial properties of CNF-AgNPs and assessed the CNF and CNF-AgNP interactions with bacteria. The attachment of AgNPs to CNFs significantly improved the stability and dispersibility of AgNPs in the bacterial growth medium compared to colloidal AgNPs. The CNF-AgNPs exerted a concentration-dependent growth-inhibitory effect on E. coli. An extracellular polysaccharide (EPS)-like structure was formed around the E. coli bacterium when incubated with a sub-lethal CNF-AgNP concentration, which led to the clustering of neighboring bacteria. No EPS-like structure was observed around the bacterium incubated with high concentration of CNF-AgNPs. Overall, this study demonstrated that CNFs significantly improved the stability and dispersibility of AgNPs in physiological medi µm, validated the antimicrobial potential of CNF-AgNPs, and provided an insight into the physio-chemical interactions between bacteria and CNF- AgNPs in a physiological growth medium. [ABSTRACT FROM AUTHOR]

Background: Overexpression and abnormal accumulation of aggregated a-synuclein (aS) have been linked to Parkinson's disease (PD) and other synucleinopathies. aS can misfold and adopt a variety of morphologies but recent studies implicate oligomeric forms as the most cytotoxic species. Both genetic mutations and chronic exposure to neurotoxins increase aS aggregation and intracellular reactive oxygen species (ROS), leading to mitochondrial dysfunction and oxidative damage in PD cell models. Results: Here we show that curcumin can alleviate aS-induced toxicity, reduce ROS levels and protect cells against apoptosis. We also show that both intracellular overexpression of aS and extracellular addition of oligomeric aS increase ROS which induces apoptosis, suggesting that aggregated aS may induce similar toxic effects whether it is generated intra- or extracellulary. Conclusions: Since curcumin is a natural food pigment that can cross the blood brain barrier and has widespread medicinal uses, it has potential therapeutic value for treating PD and other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Misfolding- and aggregation-prone proteins underlying Parkinson's, Huntington's and Machado-Joseph diseases, namely a-synuclein, huntingtin, and ataxin-3 respectively, adopt numerous intracellular conformations during pathogenesis, including globular intermediates and insoluble amyloid-like fibrils. Such conformational diversity has complicated research into amyloid-associated intracellular dysfunction and neurodegeneration. To this end, recombinant single-chain Fv antibodies (scFvs) are compelling molecular tools that can be selected against specific protein conformations, and expressed inside cells as intrabodies, for investigative and therapeutic purposes. Methodology/Principal Findings: Using atomic force microscopy (AFM) and live-cell fluorescence microscopy, we report that a human scFv selected against the fibrillar form of α-synuclein targets isomorphic conformations of misfolded polyglutamine proteins. When expressed in the cytoplasm of striatal cells, this conformation-specific intrabody co-localizes with intracellular aggregates of misfolded ataxin-3 and a pathological fragment of huntingtin, and enhances the aggregation propensity of both disease-linked polyglutamine proteins. Using this intrabody as a tool for modulating the kinetics of amyloidogenesis, we show that escalating aggregate formation of a pathologic huntingtin fragment is not cytoprotective in striatal cells, but rather heightens oxidative stress and cell death as detected by flow cytometry. Instead, cellular protection is achieved by suppressing aggregation using a previously described intrabody that binds to the amyloidogenic N-terminus of huntingtin. Analogous cytotoxic results are observed following conformational targeting of normal or polyglutamine-expanded human ataxin-3, which partially aggregate through non-polyglutamine domains. Conclusions/Significance: These findings validate that the rate of aggregation modulates polyglutamine-mediated intracellular dysfunction, and caution that molecules designed to specifically hasten aggregation may be detrimental as therapies for polyglutamine disorders. Moreover, our findings introduce a novel antibody-based tool that, as a consequence of its general specificity for fibrillar conformations and its ability to function intracellularly, offers broad research potential for a variety of human amyloid diseases. [ABSTRACT FROM AUTHOR]

Background: Overexpression and abnormal accumulation of aggregated alpha-synuclein (alphaS) have been linked to Parkinson's disease (PD) and other synucleinopathies. alphaS can misfold and adopt a variety of morphologies but recent studies implicate oligomeric forms as the most cytotoxic species. Both genetic mutations and chronic exposure to neurotoxins increase alphaS aggregation and intracellular reactive oxygen species (ROS), leading to mitochondrial dysfunction and oxidative damage in PD cell models.Results: Here we show that curcumin can alleviate alphaS-induced toxicity, reduce ROS levels and protect cells against apoptosis. We also show that both intracellular overexpression of alphaS and extracellular addition of oligomeric alphaS increase ROS which induces apoptosis, suggesting that aggregated alphaS may induce similar toxic effects whether it is generated intra- or extracellulary.Conclusions: Since curcumin is a natural food pigment that can cross the blood brain barrier and has widespread medicinal uses, it has potential therapeutic value for treating PD and other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]