 The study reports the development of a metal-organic framework, MOF, with enhanced Lewis acidity that mimics the catalytic behavior of acetylcholinesterase, AKE, and has a self-defence ability to break the activity inhibition by organophosphate compounds, OPS. The MOF-808L efficiently activates substrates and has a 2.7-fold activity improvement due to the strong polarization effect of Ul3 plus Lewis acid sites that unite highly electronegative OH groups to form the enzyme-like catalytic center. The MOF-808L is efficient in reducing neurotoxic effects and preventing neuronal tissue damage with satisfactory biosafety. This article was offered by Wachingshu, JellyCAI, YouWoo, and others.