Activation of the heat shock response as a therapeutic strategy for tau toxicity.

Alzheimer's disease is associated with the misfolding and aggregation of two distinct proteins, beta-amyloid and tau. Previously, it has been shown that activation of the cytoprotective heat shock response (HSR) pathway reduces beta-amyloid toxicity. Here, we show that activation of the HSR is also protective against tau toxicity in a cell-autonomous manner. Overexpression of HSF-1, the master regulator of the HSR, ameliorates the motility defect and increases the lifespan of transgenic C. elegans expressing human tau. By contrast, RNA interference of HSF-1 exacerbates the motility defect and shortens lifespan. Targeting regulators of the HSR also affects tau toxicity. Additionally, two small-molecule activators of the HSR, Geranylgeranylacetone (GGA) and Arimoclomol (AC), have substantial beneficial effects. Taken together, this research expands the therapeutic potential of HSR manipulation to tauopathies and reveals that the HSR can impact both beta-amyloid and tau proteotoxicity in Alzheimer's disease.

Synthesis and Characterization of Ligand-Stabilized Silver Nanoparticles and Comparative Antibacterial Activity against E. coli.

Silver is a well-established antimicrobial agent. Conjugation of organic ligands with silver nanoparticles has been shown to create antimicrobial nanoparticles with improved pharmacodynamic properties and reduced toxicity. Twelve novel organic ligand functionalized silver nanoparticles (AgNPs) were prepared via a light-controlled reaction with derivatives of benzothiazole, benzoxazine, quinazolinone, 2-butyne-1,4-diol, 3-butyne-1-ol, and heptane-1,7-dioic. UV-vis, Fourier-transform infrared (FTIR) spectroscopy, and energy-dispersive X-ray (EDAX) analysis were used to confirm the successful formation of ligand-functionalized nanoparticles. Dynamic light scattering (DLS) revealed mean nanoparticle diameters between 25 and 278 nm. Spherical and nanotube-like morphologies were observed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Seven of the twelve nanoparticles exhibited strong antimicrobial activity and five of the twelve demonstrated significant antibacterial capabilities against E. coli in a zone-of-inhibition assay. The synthesis of functionalized silver nanoparticles such as the twelve presented is critical for the further development of silver-nanoconjugated antibacterial agents.