by Keyword: Aβ
Yu, Yifan, Yu, Shilong, Battaglia, Giuseppe, Tian, Xiaohe, (2024). Amyloid‐β in Alzheimer's disease: Structure, toxicity, distribution, treatment, and prospects Ibrain 10, 266-289 
Tonelli, M, Catto, M, Sabaté, R, Francesconi, V, Laurini, E, Pricl, S, Pisani, L, Miniero, DV, Liuzzi, GM, Gatta, E, Relini, A, Gavín, R, Del Rio, JA, Sparatore, F, Carotti, A, (2023). Thioxanthenone-based derivatives as multitarget therapeutic leads for Alzheimer's disease European Journal Of Medicinal Chemistry 250, 115169
A set of twenty-five thioxanthene-9-one and xanthene-9-one derivatives, that were previously shown to inhibit cholinesterases (ChEs) and amyloid β (Aβ40) aggregation, were evaluated for the inhibition of tau protein aggregation. All compounds exhibited a good activity, and eight of them (5-8, 10, 14, 15 and 20) shared comparable low micromolar inhibitory potency versus Aβ40 aggregation and human acetylcholinesterase (AChE), while inhibiting human butyrylcholinesterase (BChE) even at submicromolar concentration. Compound 20 showed outstanding biological data, inhibiting tau protein and Aβ40 aggregation with IC50 = 1.8 and 1.3 μM, respectively. Moreover, at 0.1-10 μM it also exhibited neuroprotective activity against tau toxicity induced by okadoic acid in human neuroblastoma SH-SY5Y cells, that was comparable to that of estradiol and PD38. In preliminary toxicity studies, these interesting results for compound 20 are somewhat conflicting with a narrow safety window. However, compound 10, although endowed with a little lower potency for tau and Aβ aggregation inhibition additionally demonstrated good inhibition of ChEs and rather low cytotoxicity. Compound 4 is also worth of note for its high potency as hBChE inhibitor (IC50 = 7 nM) and for the three order of magnitude selectivity versus hAChE. Molecular modelling studies were performed to explain the different behavior of compounds 4 and 20 towards hBChE. The observed balance of the inhibitory potencies versus the relevant targets indicates the thioxanthene-9-one derivatives as potential MTDLs for AD therapy, provided that the safety window will be improved by further structural variations, currently under investigation.Copyright © 2023 Elsevier Masson SAS. All rights reserved.
JTD Keywords: a? and tau aggregation inhibition, ache and bche inhibition, aggregation, alzheimer?s disease, butyrylcholinesterase, design, drugs, dual inhibitors, fibrillization, multitarget-directed ligands (mtdls), peptide, polyphenols, potent, rivatives, Ache and bche inhibition, Alzheimer's disease, Amyloid-beta, Aβ and tau aggregation inhibition, Multitarget-directed ligands (mtdls), Thioxanthene-9-one and xanthen-9-one de, Thioxanthene-9-one and xanthen-9-one derivatives
Mir, Mònica , Tahirbegi, Islam Bogachan , Valle-Delgado, Juan José , Fernàndez-Busquets, X., Samitier, Josep , (2012). In vitro study of magnetite-amyloid β complex formation Nanomedicine: Nanotechnology, Biology, and Medicine 8, (6), 974-980
Biogenic magnetite (Fe3O4) has been identified in human brain tissue. However, abnormal concentration of magnetite nanoparticles in the brain has been observed in different neurodegenerative pathologies. In the case of Alzheimer's disease (AD), these magnetic nanoparticles have been identified attached to the characteristic brain plaques, which are mainly formed by fibrils of amyloid β peptide (Aβ). However, few clues about the formation of the magnetite-Aβ complex have been reported. We have investigated the interaction between these important players in the AD with superconducting quantum interference, scanning electron microscope, surface plasmon resonance, and magnetic force microscopy. The results support the notion that the magnetite-Aβ complex is created before the synthesis of the magnetic nanoparticles, bringing a highly stable interaction of this couple.
JTD Keywords: Alzheimer's disease, Biogenic magnetite, Amyloid β peptide (Aβ), Superconducting quantum interference, Scanning electron microscope, Surface plasmon resonance, Magnetic force microscopy
