Panoply™ Human CHRM1 Knockdown Stable Cell Line

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by neuronal degeneration and tau hyperphosphorylation. Magnolol, an active component isolated from Magnolia officinalis, has potential neuroprotective activity. However, the role and mechanism of magnolol in AD progression remain unclear. This study used bioinformatics analysis to predict biomarkers associated with AD and magnolol. The results showed that CHRM1 is a key biomarker for magnolol's anti-AD effects. Magnolol attenuates Aβ-induced SH-SY5Y cell viability inhibition, tau hyperphosphorylation, and apoptosis by upregulating CHRM1 levels. Furthermore, cAMP signaling may be a potential pathway for CHRM1 in AD. Magnolol activates the cAMP/PKA/CREB pathway by increasing CHRM1 levels. Inhibition of the cAMP/PKA/CREB pathway reverses the inhibitory effects of magnolol on Aβ-induced tau hyperphosphorylation and apoptosis in SH-SY5Y cells. In summary, magnolol alleviated Aβ-induced Tau hyperphosphorylation and neuronal apoptosis by upregulating CHRM1 and activating the cAMP/PKA/CREB pathway.

To analyze the role of magnolol in Aβ-induced neuronal injury, SH-SY5Y cells were transfected with si-con or si-CHRM1 and then treated with 10 μM magnolol and Aβ. The results showed that Aβ treatment significantly reduced CHRM1 expression and significantly increased p-Tau/Tau levels in SH-SY5Y cells (Figure 1A-C). Magnolol had little effect on CHRM1 and p-Tau/Tau levels, but it reversed the Aβ effects on these levels, while CHRM1 knockdown abolished the Aβ effects on these levels (Figure 1A-C). Furthermore, magnolol attenuated the Aβ-induced increase in cleaved-caspase-3 levels and caspase-3 activity, while CHRM1 knockdown attenuated the effects of magnolol on Aβ-stimulated SH-SY5Y cells (Figure 1D-F). Furthermore, although magnolol did not affect apoptosis under normal conditions, it attenuated Aβ-induced apoptosis, and CHRM1 knockdown reversed the inhibitory effect of magnolol on Aβ-induced apoptosis (Figure 1G, H). These results suggest that magnolol may alleviate Tau hyperphosphorylation and apoptosis by increasing CHRM1 levels in Aβ-stimulated SH-SY5Y cells.

Figure 1. Effect of magnolol on hyperphosphorylation of Tau and apoptosis in Aβ-treated SH-SY5Y cells. (Zhu G, et al., 2022)