Impaired Mitochondrial Energy Metabolism Regulated by p70S6K: A Putative Pathological Feature in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease. Mitochondrial energy metabolism and p70 ribosomal protein S6 kinase (p70S6K) play significant roles in AD pathology. However, the potential relationship between them is unclear. In this study, bioinformatics methods were initially applied to analyze the transcriptomic data in the CA1 and the primary visual cortex of patients with AD and Aß42-treated SH-SY5Y cells. By applying secreted Aß42 and p70S6K gene silencing in cells, we explored disorders in mitochondrial function and the regulatory roles of p70S6K by flow cytometry, laser scanning confocal microscopy, high-performance liquid chromatography, Western blotting, and quantitative reverse transcription PCR. The study reveals that impaired mitochondrial energy metabolism is a potential pathological feature of AD and that p70S6K gene silencing reversed most of the changes induced by Aß42, such as the activities of the electron transport chain complexes I and III, as well as ATP synthase, ATP production, generation of reactive oxygen species, mitochondrial membrane potential, and phosphorylation of AMPK, PINK1, and Parkin, all of which are required for mitochondria to function properly in the cell.

A Molecular Integrative Study on the Inhibitory Effects of WRR and ERW on Amyloid ß Peptide (1-42) Polymerization and Cell Toxicity.

Alzheimer's disease (AD) is a neurodegenerative disease and the main pathological characteristic of AD is the deposition of Aß42 in the brain. Inhibition of Aß42 polymerization is one of the important research directions. Due to the pathological complexity of Alzheimer's disease, studies on Aß42 polymerization inhibitors have not made significant progress worldwide. Using an independently constructed structure database of oligopeptides, in this study, molecular docking, umbrella sampling analysis of free energy, ThT fluorescence detection of Aß42 polymerization, transmission electron microscopy, and flow cytometry detection of reactive oxygen species (ROS) and apoptosis were performed to screen tripeptides and pentapeptides that inhibit polymerization. It was found that two tripeptides, i.e., WRR and ERW, bind stably to the core of Aß42 polymerization in the molecular dynamics analysis, and they significantly inhibited the aggregation of Aß42 and reduced their cell toxicity in vitro.

Effect of Breeding Season on Haemosporidian Infections in Domestic Chickens.

Reproduction is believed to contribute to the frequently observed seasonal cycles in parasite loads in many organisms, as an investment in reproduction by the host could result in a higher susceptibility to parasites. In this study, we examined the impact of breeding season on haemosporidian infection in free-range chickens (Gallus gallus domesticus). We sampled a total of 122 chickens (66 chickens during the breeding season of April 2017 and 56 chickens during the non-breeding season of January 2017) to test for haemosporidian infections. The result showed that 56 out of 66 chickens examined during the breeding season tested positive for parasites (84.8% parasite prevalence), whereas 39 out of 56 chickens tested positive for parasites during the non-breeding season (69.6% parasite prevalence). Moreover, among the 11 Leucocytozoon lineages and 2 Plasmodium lineages identified, the parasite lineages that infected chickens during the breeding season were more diversified than those that affected chickens during the non-breeding season. This study indicated that chickens have a higher incidence of haemosporidian infection and a greater diversity of haemosporidian parasite lineages during the breeding season relative to the non-breeding season.