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Page 24 of 24 Neuroimmunol Neuroinflammation 2019;6:15 I http://dx.doi.org/10.20517/2347-8659.2019.019

a binding site of Aβ with AChE. Our previous study found for the first time that the 7-20 amino acid region
on the N-terminal of AChE (AChE7-20) can induce the formation of Aβ oligomer. However, the binding
mode and pathophysiological effects of AChE7-20 and Aβ interaction remains unclear. In this study,
protein-protein docking and molecular dynamics simulation were used to probe the interaction between
AChE7-20 and Aβ. The residues of Arg13, Glu7, and Arg18 on AChE7-20 were the main contacts of
AChE7-20 with Aβ. His13/14, Glu22/Asp23, and Asn27 on α-helix Aβ and Glu11, Phe19/20, Glu22/Asp23,
and Met35 on β-sheet Aβ were the key residues of Aβ binding with AChE7-20, respectively. Compared
with Aβ alone, AChE7-20-Aβ interaction triggered the transformation of Aβ from α helix to β sheet. The
residues of Aβ participating in aggregation became fluctuant due to the presence of AChE7-20. The TEM
morphology of Aβ aggregation confirmed that AChE7-20 induced more Aβ fibrils than control AChE7-
20 in scramble sequence (Sc-AChE7-20). The binding affinity of AChE7-20 with Aβ oligomer was higher
than Sc-AChE7-20 determined by SPR assay. Compared with Aβ alone, AChE7-20 co-incubation enhanced
the apoptosis of primary hippocampal neurons induced by Aβ. Intervention of AChE-Aβ interaction was
further studied with Bis-(9)-(-)-Meptazinol (BisMep), a novel dual-binding AChE inhibitor developed by
our group. Results of molecular docking suggested that BisMep could not only interact with Tyr341 and
Asp74 residues in the PAS of AChE through hydrogen bond and ionic bond, but also Arg13 and Arg16
residues in AChE7-20 through H-π and cation-π interaction, which are the key residues in AChE7-20-
Aβ interaction. Subsequently, in Aβ-induced AD model mice, BisMep could significantly decrease the Aβ
deposits, the activation of astrocytes and microglia, the levels of pro-inflammatory factors, and the AChE
catalytic activity in the hippocampus, and eventually improve the performance of learning and memory of
AD model mice. In conclusion, this study revealed the key residues and binding mode between AChE7-
20 and Aβ and confirmed the triggering effect of AChE7-20 on Aβ aggregation and neurotoxicity, which
provided structural biological information for the discovery of a lead compound intervening AChE-Aβ
interaction.

34. Perceptual closure analysis: preliminary study with event-related potentials

Serrano-Juárez Carlos Alberto

Laboratorio de Neurometría, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de
México, México

The perceptual closure is a complex visual skill that allows perceiving an incomplete pattern or object as
complete or whole. A better knowledge of the electrophysiological bases of the perceptual closure would
be useful to better understand the visuospatial alterations that occur in pathologies such as Williams
syndrome, schizophrenia, and autism. Event-related potentials (ERP) studies in tasks with fragmented
objects or faces have evidenced the presence of a component called Closure Negativity.

The objective of this study was to identify differences in ERP obtained from correctly or incorrectly
fragmented figures in a perceptual closure task. Participants were 12 healthy male adults, university
students between 20 and 31 years of age, who performed a visual closure task in which they had to decide
if an incomplete figure corresponded (congruent condition) or not (incongruent condition) to a complete
figure that was presented before. ERPs were recorded in 32 electrodes with a NeuroScan equipment.
The ERP showed a negative peak around 170 ms (N1) without differences between the conditions, and a
positive peak between 240 and 270 ms (P2) with greater amplitude for the incongruent condition than for
the congruent one. Additionally, a negativity was observed around 400 ms that also had a greater amplitude
for the incongruent vs. congruent condition. These preliminary findings give evidence of a differentiated
processing for figures perceived as congruent vs. incongruent from a pattern, in latencies that could be
related to late visual processing (P2) and probably to a perceptual semantic evaluation. This pattern should
be confirmed with more studies, to be applied later in clinical populations such as those mentioned.