Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against ␤-amyloid (A␤) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against A␤ (NAbs-A␤) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-A␤ recognized the mid-/Cterminal end of A␤ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-A␤ were able to interfere with A␤ peptide toxicity, but NAbs-A␤ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-A␤ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-A␤ to dispose of proteins or peptides that are prone to forming toxic aggregates.

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The development of earth-friendly efficient electrocatalysts for the oxygen evolution reaction (OER) becomes crucial for renewable energy production. In this work, green synthesized reduced cobalt ferrocyanide at different time intervals (RCFC-t) was demonstrated as an effective and long-lasting electrocatalyst for the OER process. The RCFC-10 loaded glassy carbon electrode runs at an overpotential of 321 mV (1.55 V) at 10 mA cm–2, and a lower overpotential of 291 mV exhibited by the optimal RCFC-10/nickel foam was almost comparable to the benchmark catalyst, such as IrO2. This newborn RCFC-10 shows excellent OER performance and durability over 250 h with 4.1% potential loss in alkaline medium. At 1.58 V, the solar-driven water electrolysis demonstration supports the efficiency of a newborn electrocatalyst in solar-to-hydrogen conversion. These research findings confirm that low-cost greener synthesized RCFC-10/NF can be used for large-scale hydrogen generation.

There is evidence that naturally occurring antibodies directed against Aβ (nAbs-Aβ) have a role in Aβ-metabolism and Aβ-clearance. The presence of nAbs-Aβ leads to a reduction in amyloid fibrillation and thus a reduction in their toxicity. We investigated the effects of nAbs-Aβ in respect to oligomerization and used the Tg2576 transgenic mouse model in order to investigate the rapid effect with a single-dose (24 h) on oligomer breakdown and cytokine secretion along with immunohistochemical characterization of synaptic plasticity. nAbs-Aβ were able to reduce toxic oligomer concentration with an increase in Aβ-monomers. Cytokine secretion was significantly reduced. Synaptic plasticity was also improved after administration of nAbs. Finally, single treatment lead to a significant improvement in cognition. This study demonstrates the efficacy of nAbs-Aβ and presents evidence that several hallmarks of the disease are targeted by nAbs-Aβ.

BackgroundStudies of the role of the cytokine macrophage-migration-inhibitory-factor (MIF) in malignant tumors have revealed its stimulating influence on cell-cycle progression, angiogenesis and anti-apoptosis.ResultsHere we show that in vitro targeting MIF in cultures of human malignant glioblastoma cells by either antisense plasmid introduction or anti-MIF antibody treatment reduced the growth rates of tumor cells. Of note is the marked decrease of proliferation under confluent and over-confluent conditions, implying a role of MIF in overcoming contact inhibition. Several proteins involved in contact inhibition including p27, p21, p53 and CEBPalpha are upregulated in the MIF antisense clones indicating a restoration of contact inhibition in the tumor cells. Correspondingly, we observed a marked increase in MIF mRNA and protein content under higher cell densities in LN18 cells. Furthermore, we showed the relevance of the enzymatic active site of MIF for the proliferation of glioblastoma cells by using the MIF-tautomerase inhibitor ISO-1.ConclusionOur study adds another puzzle stone to the role of MIF in tumor growth and progression by showing the importance of MIF for overcoming contact inhibition.