New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models

Figure 3

Neuroprotective effects of LM-031 and licochalcone A in TBP/Q₇₉-GFP-expressing SH-SY5Y cells. (a) Experimental flow chart. TBP/Q₇₉-GFP SH-SY5Y cells were plated on dishes with retinoic acid (10 μM) added on day 1 to initiate neuronal differentiation. On the next day, LM-031 or licochalcone A (100 nM) was added to the cells for 8 h followed by inducing TBP/Q₇₉-GFP expression with doxycycline (5 μg/mL) for 6 days. Aggregation, neurite outgrowth (by HCA), and caspase 3 activity were assessed. (b) Relative aggregation, (c) neuronal outgrowth, and (d) caspase 3 activity of TBP/Q₇₉-GFP-expressing SH-SY5Y cells with LM-031 or licochalcone A treatment (). values: comparisons between treated and untreated cells (, , ) or between untreated and uninduced cells (^##). (e) Representative microscopy images of differentiated TBP/Q₇₉-GFP-expressing SH-SY5Y cells untreated or treated with LM-031 or licochalcone A, with nuclei counterstained in blue (top row), aggregates marked in red (middle row), or neurites and cell bodies outlined in red for outgrowth quantification (bottom row).

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