AChE, acetylcholinesterase; AChEIs, acetylcholinesterase inhibitors; AChT, acetylthiocholine; AD, Alzheimer's disease; ADME, absorption, distribution, metabolism and excretion; Acetylcholinesterase; Alzheimer's disease; BBB, blood brain barrier; Ca2+, calcium; ChE, Cholinesterases; DMEM, Dulbecco's modified Eagle's medium; DTNB, 5,5-dithiobis-(2-nitrobenzoic acid); ENM, elastic network modeling; ER, endoplasmic reticulum; FRET, fluorescence resonance energy transfer; G6PD, glucose-6-phosphate dehydrogenase; HBSS, Hank's balanced salt solution; IP, intraperitoneal; LBD, Ligand binding domain; LC-MS, Liquid chromatography-mass spectrometry; LiCABEDS, Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps; MAP2, microtubule associated protein 2; MD, Molecular dynamics; MTDLs; MTDLs, multi-target directed ligands; MWM, Morris water maze; NBM, neurobasal medium; NMA, normal mode analysis; NMDA receptor; NMDAR, N-methyl-D-aspartate receptor; Neuroprotection; OPLS, Optimized potential for liquid simulations; PBS, phosphate-buffered saline; PFA, paraformaldehyde; Polypharmacology; RMSD, root mean square deviation; SAR, structure-activity relationships; SD, standard deviation; SVM, support vector machine; Structure-based drug design; TBI, traumatic brain injury; TMD, transmembrane domain; Tacrine; h-NMDAR, human NMDAR; hAChE, human AChE; ppm, parts per million