Caprylic acid attenuates amyloid-ß proteotoxicity by supplying energy via ß-oxidation in an Alzheimer's disease model of the nematode Caenorhabditis elegans.

Computer-based analysis of motility was used as a measure of amyloid-ß (Aß) proteotoxicity in the transgenic strain GMC101, expressing human Aß1-42 in body wall muscle cells. Aß-aggregation was quantified to relate the effects of caprylic acid (CA) to the amount of the proteotoxic protein. Gene knockdowns were induced through RNA-interference (RNAi). Moreover, the estimation of adenosine triphosphate (ATP) levels, the mitochondrial membrane potential (MMP) and oxygen consumption served the evaluation of mitochondrial function. CA improved the motility of GMC101 nematodes and reduced Aß aggregation. Whereas RNAi for orthologues encoding key enzymes for α-lipoic acid and ketone bodies synthesis did not affect motility stimulation by CA, knockdown of orthologues involved in ß-oxidation of fatty acids diminished its effects. The efficient energy gain by application of CA was finally proven by the increase of ATP levels in association with increased oxygen consumption and MMP. In conclusion, CA attenuates Aß proteotoxicity by supplying energy via FAO. Since especially glucose oxidation is disturbed in Alzheimer´s disease, CA could potentially serve as an alternative energy fuel.

Fast and sustainable planar yeast-based bioassay for endocrine disruptors in complex mixtures: Start of cell cultivation to result within one day.

High-performance thin-layer chromatography hyphenated with planar multiplex bioassays and high-resolution tandem mass spectrometry contributes to the non-target detection or even identification of active compounds in complex mixtures such as food, feed, cosmetics, commodities, and environmental samples. It can be used to discover previously unknown harmful or active substances in complex samples and to tentatively assign molecular formulas. This method is already faster than the commonly used in vitro assays along with liquid chromatographic separations, but overnight cell cultivation still prevents a planar bioassay from being performed within one day. There is also still potential for optimization in terms of sustainability. To achieve this, the planar bioassay protocols for the detection of androgen-like and estrogen-like compounds were harmonized. The successful minimization of the cell culture volume enabled accelerated cell cultivation, which allowed the bioassay to be performed within one day. This was considered a milestone achieved, as up to 23 samples per plate can now be analyzed from the start of cultivation to the biological endpoint on the same day. Doubling the substrate amount and increasing the pH of the silica gel layer led to a more sensitive and selective bioassay due to the enhanced fluorescence of the formed end-product. The faster and more sustainable bioassay protocol was applied to complex samples such as sunscreen and red wine to detect estrogen-like compounds. The developed method was validated by comparison with a standard method.