AChE and BChE are hydrolases of the neurotransmitter acetylcholine (ACh). Alzheimer’s disease is a devastating neurodegenerative disease characterized by memory and cognitive decline. Specifically, Its pathological pathway also involves the deposition of amyloid-β (Aβ), abnormal tau protein, neuronal apoptosis, etc. Therefore, Alzheimer’s disease is accompanied by decreased levels of acetylcholine (ACh), which exacerbates Aβ toxicity. In contrast, AChE inhibitors stimulate cholinergic receptors and reduce the hydrolysis of acetylcholine (ACh). Here, we’ll introduce MR2938, an AChE/BChE inhibitor with anti-neuroinflammatory and neuroprotective effects.

MR2938 is a dual AChE and BChE inhibitor with anti-neuroinflammatory activity and neuroprotective effects.

MR2938 is a multifunctional neuroprotective agent. It (20 μM) has double inhibitory activity on AChE and BChE, with inhibition rates of 91.8% and 38.7%, respectively.

Microglia are activated by NLRP3 activation and stimulation by pro-inflammatory cytokines. In microglia BV-2, MR2938 (2.5 μM; 24 h) decreases the levels of proinflammatory cytokines NO, IL-1β, CCL2, IL-6, and TNF-α. It (10 μM; 24 h) also reduces LPS (1 μg/mL; 24 h)-induced NLRP3 expression and JNK phosphorylation levels. It inhibits MAPK/JNK signaling pathway and bind upstream molecules to inhibit inflammatory response. On another hand, NF-κB appears mainly as inactive dimers of the p50 and p65 subunits. In addition, MR2938 decreases total p65 and phosphorylated p65 (p-p65) levels in BV2 cells. It can inhibit inflammatory cytokines by inhibiting NF-κB pathway. However, MR2938(2.5-10 μM; 24 h) shows little cytotoxicity to BV2 and did not significantly inhibit cell viability.

In conclusion, MR2938 is a potent inhibitor with neuroprotective effects. And also, it can inhibit the NF-κB and MAPK/JNK signaling pathways to inhibit inflammation.


[1] Lv L, et al. Eur J Med Chem. 2023 Jun 5;254:115346.