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Peer-reviewed

Dual Inhibitors of Amyloid-β and Tau Aggregation with Amyloid-β Disaggregating Properties: Extended <i>In Cellulo</i>, <i>In Silico</i>, and Kinetic Studies of Multifunctional Anti-Alzheimer’s Agents

Anna Pasieka, Dawid Panek, Natalia Szałaj, Alba Espargaró, Anna Więckowska, Barbara Malawska, Raimon Sabaté, Marek Bajda

ACS Chemical Neuroscience · 2021

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Summary

In Alzheimer's disease, neurons slowly degenerate due to the accumulation of misfolded amyloid β and tau proteins. In our research, we performed extended studies directed at amyloid β and tau aggregation inhibition using <i>in cellulo</i> (<i>Escherichia coli</i> model of protein aggregation), <i>in silico</i>, and <i>in vitro</i> kinetic studies. We tested our library of 1-benzylamino-2-hydroxyalkyl multifunctional anti-Alzheimer's agents and identified very potent dual aggregation inhibitors. Among the tested derivatives, we selected compound <b>18</b>, which exhibited a unique profile of biological activity. This compound was the most potent and balanced dual aggregation inhibitor (Aβ<sub>42</sub> inhibition (inh.) 80.0%, tau inh. 68.3% in 10 μM), with previously reported <i>in vitro</i

Source type
Peer-reviewed study
DOI
10.1021/acschemneuro.1c00235
Catalogue ID
SNmoi53kzx-1b7zgb
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