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  • DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons.

DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons.

ACS central science (2021-11-30)
Claire E McGhee, Zhenglin Yang, Weijie Guo, Yuting Wu, Mingkuan Lyu, Cynthia J DeLong, Shanni Hong, Yuan Ma, Melvin G McInnis, K Sue O'Shea, Yi Lu
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Lithium has been a drug for bipolar disorders (BD) for over 70 years; however, its usage has been limited by its narrow therapeutic window (between 0.6 and 1.2 mM). Understanding the cellular distribution of lithium ions (Li+) in patient cells will offer deep insight into this limitation, but selective imaging of Li+ in living cells under biomedically relevant concentration ranges has not been achieved. Herein, we report in vitro selection and development of a Li+-specific DNAzyme fluorescent sensor with >100-fold selectivity over other biorelevant metal ions. This sensor allows comparative Li+ visualization in HeLa cells, human neuronal progenitor cells (NPCs), and neurons derived from BD patients and healthy controls. Strikingly, we detected enhanced accumulation of Li+ in cells derived from BD patients compared with healthy controls in differentiated neurons but not NPCs. These results establish the DNAzyme-based sensor as a novel platform for biomedical research into BD and related areas using lithium drugs.

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γγ-Sekretase-Inhibitor XXI, Verbindung E, This g-secretase inhibitor, CAS 209986-17-4, is a cell-permeable, potent, selective, non-transition-state analog inhibitor of γ-secretase and Notch processing. Lowers Aβ levels in APP transgenic mice