Neurophysiological indicators of Alzheimer’s disease include the presence of aggregated amyloid-beta (Aβ) peptide plaques and low levels of the neurotransmitter, acetylcholine, resulting in cognitive impairment.
Acetylcholinesterase has been implicated in not only the aggregation of extracellular Aβ peptides through the enzyme’s
peripheral anionic site, but also the hydrolysis of acetylcholine at its catalytic active site. Two components in a methanolic
extract of black walnuts (Juglians nigra), gallic and ellagic acids, were found to prevent aggregation of Aβ peptides in the
presence of acetylcholinesterase and to disaggregate previously formed oligomers. In addition, both compounds inhibited
acetylcholinesterase activity, thus retaining higher acetylcholine concentrations. Analysis of phenolic structures related to
gallic acid indicated that 1,3,5-trisubstituted phenolic rings conferred these inhibitory effects on acetylcholinesterase, and
thus may provide a structural model on which to design dual inhibitors for both acetylcholinesterase catalytic activity and
Aβ aggregation and disaggregation.
Keywords: Acetylcholinesterase, aggregation, amyloid-beta, phenol, dual inhibitors, Alzheimer’s disease.
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