Fig. 3 Identification of KEECs that increase KCC2 expression in human RTT neurons. Identification of KEECs that increase KCC2 expression in human RTT neurons.

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Fig. 3 Identification of KEECs that increase KCC2 expression in human RTT neurons. Identification of KEECs that increase KCC2 expression in human RTT neurons. (A) B score rank of 929 small-molecule compounds from LINCS, SMART, and ICCB drug libraries; B score >3 indicates compounds potentially increasing KCC2 expression. (B) KCC2 reporter activity induced by the most significant compounds identified from the RTT neuron screening. Compound data were color-coded according to their library of origin: LINCS (red), SMART (yellow), and ICCB (blue). (C to H) KCC2 protein expression induced by KEEC KW-2449 (n = 4), BIO (n = 3), crenolanib (n = 4), indirubin monoxime (n = 4), XL-184 (n = 4), and FLT3 inhibitor-1 (n = 4) in cultured human RTT neurons. (I) KCC2 protein expression induced by treatment of RTT neurons with resveratrol, a SIRT1 activator (n = 2), and by co-application of the SIRT1 pathway inhibitor EX-527 (n = 2). (J) Dose-dependent KCC2 protein expression induced by treatment of RTT neurons with piperine (n = 2). (K) KCC2 protein expression induced by treatment of RTT neurons with piperine, a TRPV1 activator (n = 2), and by co-application of the TRPV1 antagonist A784168 (n = 2). Data are means ± SEM. *P < 0.05 and **P < 0.01, Student’s t test. Xin Tang et al., Sci Transl Med 2019;11:eaau0164 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works