In Vitro Effect of H2O2, Some Transition Metals and Hydroxyl Radical Produced Via Fenton and Fenton-Like Reactions, on the Catalytic Activity of AChE and the Hydrolysis of ACh

It is well known that the principal biomolecules involved in Alzheimer's disease (AD) are acetylcholinesterase (AChE), acetylcholine (ACh) and the amyloid beta peptide of 42 amino acid residues (A beta 42). ACh plays an important role in human memory and learning, but it is susceptible to hydrolysis by AChE, while the aggregation of A beta 42 forms oligomers and fibrils, which form senile plaques in the brain. The A beta 42 oligomers are able to produce hydrogen peroxide (H2O2), which reacts with metals (Fe2+, Cu2+, Cr3+, Zn2+, and Cd2+) present at high concentrations in the brain of AD patients, generating the hydroxyl radical (-OH) via Fenton (FR) and Fenton-like (FLR) reactions. This mechanism generates high levels of free radicals and, hence, oxidative stress, which has been correlated with the generation and progression of AD. Therefore, we have studied in vitro how AChE catalytic activity and ACh levels are affected by the presence of metals (Fe3+, Cu2+, Cr3+, Zn2+, and Cd2+), H2O2 (without A beta 42), and -OH radicals produced from FR and FLR. The results showed that the H2O2 and the metals do not modify the AChE catalytic activity, but the -OH radical causes a decrease in it. On the other hand, metals, H2O2 and -OH radicals, increase the ACh hydrolysis. This finding suggests that when H2O2, the metals and the -OH radicals are present, both, the AChE catalytic activity and ACh levels diminish. Furthermore, in the future it may be interesting to study whether these effects are observed when H2O2 is produced directly from A beta 42.