Fig. 2: Hit3 improves survival and function of hiMNs from diverse human patients. | Cell Death & Disease

Fig. 2: Hit3 improves survival and function of hiMNs from diverse human patients.

From: Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease

Fig. 2: Hit3 improves survival and function of hiMNs from diverse human patients.The alternative text for this image may have been generated using AI.

A Dose-dependent effects of the indicated chemicals on hiMNs from diverse ALS patients at 1 week post replating on astrocytes (mean ± SEM; n = 4 independent samples at each concentration). B Hit3 outperforms the positive control Ken in promoting survival of diverse ALS-hiMNs at 1 week post replating on astrocytes (mean ± SEM; n = 4 independent samples for each group; *p < 0.05, **p < 0.01 and ****p < 0.0001 when compared to the Ken-treated samples, Student’s t-test). C Hit3 and the positive control Ken increased neuronal soma size and complexity of ALS1- and ALS4-hiMNs at 52 dpi. Scale bar, 50 µm. D Quantification of neuronal soma size (mean ± SEM; n = 3 independent samples; ALS1 group: n = 80 for Veh, n = 71 for Ken, n = 93 for Hit3; ALS4 group: n = 95 for Veh, n = 70 for Ken, n = 76 for Hit3; **p < 0.01 and ***p < 0.001 when compared to the vehicle group, Student’s t-test). E, F Hit3 and the positive control Ken rescued the ability of ALS-hiMNs to form neuromuscular junctions (NMJs, indicated by arrows) on co-cultured myotubes. NMJ frequencies were indicated as percentage values over 100 hiMN network-associated myotubes counted for each group. Scale bar 10 µm. SYN1 Synapsin 1, a-BTX a-bungarotoxin, MHC myosin heavy chain.

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