Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC<sub>50</sub>, 19.7 nM for hAChE and 0.66 μM for hBuChE) and the good Aβ aggregation inhibition (49.2% at 20 μM), and it was also a good antioxidant (1.26 trolox equivalents).
The amyloid beta (1-42)-induced modification of the balance oxidant-antioxidant and acetylcholinesterase action in the hippocampus of the rat has been ameliorated using the essential oil.
β-Secretase (BACE1) and acetylcholinesterase (AChE), which are required for the production of neurotoxic β-amyloid (Aβ) and the promotion of Aβ fibril formation, respectively, are considered as prime therapeutic targets for AD.
Furthermore, the results of ELISA and western blot analysis demonstrated that EGCG administration restored acetylcholinesterase activity and modulated the expression levels of neuronal nitric oxide synthase (nNOS), β‑amyloid and amyloid precursor protein in anesthesia‑induced mice.
Acetylcholinesterase (AChE), which is most widely known for the hydrolysis of the neurotransmitter acetylcholine, has a peripheral allosteric subsite responsible for amyloidosis in Alzheimer's disease through interaction with amyloid β-peptide.
The biological assays indicated that most of them showed potent inhibition and excellent selectivity towards acetylcholinesterase (AChE), and could inhibit self-induced β-amyloid (Aβ) aggregation.
Cordycepin inhibits ROS production, elevated levels of Ca<sup>2+</sup> induced by Aβ<sub>25-35</sub>, and the activation of acetylcholinesterase; all these are involved in oxidative-induced apoptosis.
In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase and self-induced β-amyloid (Aβ) aggregation, and moderate antioxidant activity.
Brain tissues were collected to measure Aβ levels (Aβ<sub>1-40</sub> and Aβ<sub>1-42</sub>), acetylcholine (ACh), acetylcholinesterase (AChE), nitric oxide (NO), lipid peroxidation (LPO), antioxidant activities, cyclooxygenases (COX) and cytokines (IL-1α, IL-1β and IL-6), while plasma was collected to measure TGF-1β.
Specifically, acetylcholinesterase inhibitors were prescribed to 67% of the amyloid-positive and 27% of the amyloid-negative subjects in the information group compared with 56 and 43%, respectively, in the control group (p < 0.0001).
The new molecules were able to target the cholinergic system, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit amyloid-β aggregation.
The Aβ42-induced PS1 increase was abolished by siRNA AChE pretreatment, suggesting that AChE may participate in the pathological feedback loop between PS1 and Aβ.