Glucosylpolyphenols as Inhibitors of Aβ-Induced Fyn Kinase Activation and Tau Phosphorylation: Synthesis, Membrane Permeability, and Exploratory Target Assessment within the Scope of Type 2 Diabetes and Alzheimer's Disease

Despite the rapidly increasing number of patients suffering from type 2 diabetes, Alzheimer's disease, and diabetes-induced dementia, there are no disease-modifying therapies that are able to prevent or block disease progress. In this work, we investigate the potential of nature-inspired glucosylpolyphenols against relevant targets, including islet amyloid polypeptide, glucosidases, and cholinesterases. Moreover, with the premise of Fyn kinase as a paradigm-shifting target in Alzheimer's drug discovery, we explore glucosylpolyphenols as blockers of Aβ-induced Fyn kinase activation while looking into downstream effects leading to Tau hyperphosphorylation. Several compounds inhibit Aβ-induced Fyn kinase activation and decrease pTau levels at 10 μM concentration, particularly the per-O-methylated glucosylacetophloroglucinol and the 4-glucosylcatechol dibenzoate, the latter inhibiting also butyrylcholinesterase and β-glucosidase. Both compounds are nontoxic with ideal pharmacokinetic properties for further development. This work ultimately highlights the multitarget nature, fine structural tuning capacity, and valuable therapeutic significance of glucosylpolyphenols in the context of these metabolic and neurodegenerative disorders.European Commission GA 612347Fundação para a Ciência e a Tecnologia SFRH/BD/93170/2013, SFRH/BD/116614/2016, PD/BD/142847/2018, SFRH/BD/145600/2019, CEECIND/03414/2018, CEECIND/02300/2017, UIDB/00100/2020, UIDB/04046/2020, UIDB/04378/2020, IF/00780/2015Gobierno de España CTQ2016-78703-PJunta de Andalucía FQM13

Cosmological consequences of a Chaplygin gas dark energy

A combination of recent observational results has given rise to what is currently known as the dark energy problem. Although several possible candidates have been extensively discussed in the literature to date the nature of this dark energy component is not well understood at present. In this paper we investigate some cosmological implications of another dark energy candidate: an exotic fluid known as the Chaplygin gas, which is characterized by an equation of state $p = -A/\rho$, where $A$ is a positive constant. By assuming a flat scenario driven by non-relativistic matter plus a Chaplygin gas dark energy we study the influence of such a component on the statistical properties of gravitational lenses. A comparison between the predicted age of the universe and the latest age estimates of globular clusters is also included and the results briefly discussed. In general, we find that the behavior of this class of models may be interpreted as an intermediary case between the standard and $\Lambda$CDM scenarios.Comment: 7 pages, 5 figures, to appear in Phys. Rev.

Search for an invisibly decaying Higgs boson or dark matter candidates produced in association with a Z boson in pp collisions at root s=13 TeV with the ATLAS detector

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