Clusterin levels in undernourished SH-SY5Y cells.

Food-related disorders are increasingly common in developed societies, and the psychological component of these disorders has been gaining increasing attention. Both overnourishment with high-fat diets and perinatal undernourishment in mice have been linked to a higher motivation toward food, resulting in an alteration in food intake. Clusterin (CLU), a multifaced protein, is overexpressed in the (NAc) of over-fed rats, as well as in those that suffered chronic undernutrition.

Trehalose-based neuroprotective autophagy inducers.

A small set of trehalose-centered putative autophagy inducers was rationally designed and synthesized, with the aim to identify more potent and bioavailable autophagy inducers than free trehalose, and to acquire information about their molecular mechanism of action. Several robust, high yield routes to key trehalose intermediates and small molecule prodrugs (2-5), putative probes (6-10) and inorganic nanovectors (12a - thiol-PEG-triazole-trehalose constructs 11) were successfully executed, and compounds were tested for their autophagy-inducing properties. While small molecules 2-11 showed no pro-autophagic behavior at sub-millimolar concentrations, trehalose-bearing PEG-AuNPs 12a caused measurable autophagy induction at an estimated 40 μM trehalose concentration without any significant toxicity at the same concentration.

Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis.

Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the cell, requiring the use of carriers to protect them from degradation and transporting them across the cell membrane.

Knocking down HMGB1 using dendrimer-delivered siRNA unveils its key role in NMDA-induced autophagy in rat cortical neurons.

Purpose: To explore the role of the High Mobility Group Box 1 (HMGB1) protein in NMDA-mediated excitotoxicity in rat cortical neurons.

Methods: We knocked down HMGB1 using small-interfering RNA (siRNA) delivered into neurons by means of a dendrimer. We determined autophagy activation by measuring the ratio of light chain 3 protein isoforms (LC3B-I)/LC3B-II and by determining autophagolysosome labeling using the specific marker monodansyl cadaverine.

Dendrimer-mediated siRNA delivery knocks down Beclin 1 and potentiates NMDA-mediated toxicity in rat cortical neurons.

Autophagy is an important process which plays a key role in cellular homeostasis by degrading cytoplasmic components in the lysosomes, which facilitates recycling. Alterations to normal autophagy have been linked to excitotoxicity, but the mechanisms governing its signal transduction remain unclear. The aim of this study was to explore the role of autophagy in neuronal excitotoxic death by delivering small interfering RNA (siRNA) to rat cortical neurons, using a dendrimer to silence the autophagy-related gene 6 (beclin 1) and to determine the role of autophagy in excitotoxicity.

Inhibition of p42 MAPK using a nonviral vector-delivered siRNA potentiates the anti-tumor effect of metformin in prostate cancer cells.

Aims: The aim of this work was to study if a G1-polyamidoamine dendrimer/siRNA dendriplex can remove the p42 MAPK protein in prostate cancer cells and to potentiate the anti-tumoral effect of the antidiabetic drug metformin and taxane docetaxel.

Material & Methods: The dendriplex uptake was studied using flow cytometry analysis. Transfection efficiency was determined by measuring p42 MAPK mRNA and protein levels.

Atorvastatin reduces high glucose toxicity in rat peritoneal mesothelial cells.

Objective: Continuous exposure of the peritoneal membrane to high glucose dialysis solutions can produce functional alterations in this membrane. We studied the toxic effects of high glucose (50 mmol/L and 83 mmol/L) and its reversal by atorvastatin (0.5 - 5 μmol/L) on cultures of rat peritoneal mesothelial cells (PMCs).