Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases.

Metal-organic frameworks (MOFs) have been shown to be great alternatives to traditional porous materials in various chemical applications, and they have been very widely studied for biomedical applications in the past decade specifically for drug storage. After our review published in 2011 [Keskin and Kızılel, Ind. Eng. Chem. Res. 2011, 50 (4), 1799-1812, 10.1021/ie101312k], we have witnessed a very fast growth not only in the number and variety of MOFs but also in their usage across a broad spectrum of biomedical fields. With the recent integration of molecular modeling and data science approaches to the experimental studies, biomedical applications of MOFs have been significantly accelerated positioning them as pivotal components in the regenerative medicine, medical imaging, and diagnostics. In this review, we visited the diverse biomedical applications of MOFs considering the recent experimental and computational efforts on drug storage and delivery, bioimaging, and biosensing. We focused on the underlying mechanisms governing the molecular interactions between MOFs and biological systems and discussed both the opportunities and challenges in the field to highlight the potential of MOFs in advanced therapeutics for cancer and neurological diseases.