Abstract
We found a significant inhibitory effect of alpha-tocopherol (TPh) on soluble commercial preparations of acetylcholinesterase (AChE), that is, human recombinant AChE (hAChE) and AChE from the electric eel. The inhibition occurs via the interaction of the phytol chain with the peripheral anionic site of AChE. However, TPh fails to inhibit the molecular forms of the enzyme that are important for the development of Alzheimer’s disease, in particular, AChE in erythrocytes and cholinergic membrane-bound AChE in the mouse brain, while the latter is even activated with the administration of TPh in vivo. When selecting a model for screening the substances with anticholinesterase properties for the development of new anti-AD therapies, it should be noted that the inhibition of commercial preparations of enzymes may not necessarily be indicative of an anticholinesterase effect in the body.
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Abbreviations
- ACh:
-
acetylcholine
- ATCh:
-
acetylthiocholine
- AChE:
-
acetylcholinesterase
- hAChE:
-
human recombinant AChE
- AD:
-
Alzheimer’s disease
- BTCh:
-
butyrylthiocholine
- BChE:
-
butyrylcholinesterase
- DTNB:
-
5;5’-dithiobis(2-nitrobenzoic acid)
- OS:
-
oxidative stress
- PAS:
-
peripheral anionic site
- LPO:
-
lipid peroxidation
- TPh:
-
alpha-tocopherol
- GPI:
-
glycosylphosphatidylinositol
- PRiMA:
-
proline-rich membrane anchor
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Molochkina, E.M., Treshchenkova, Y.A. The Effect of Alpha-Tocopherol on the Activity of Acetylcholinesterases from Different Sources. Neurochem. J. 13, 36–42 (2019). https://doi.org/10.1134/S1819712419010161
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DOI: https://doi.org/10.1134/S1819712419010161