Study of Effect of a New Curcumin Derivative on Formation of Toxic aAggregates and Prevention of Learning and Spatial Memory Impairment in Male Wistar Rats

Backgrounds & Aggregates of β-amyloid protein are the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit Aβ fibrils formation and or reduce their associated neurotoxicity might have therapeutic values for treating AD. Although curcumin has shown promising therapeutic utilities for many diseases, including Alzheimer, its clinical application is severely limited because of its poor stability under physiological conditions. In this study, the inhibitory effects of 2,6-bis(3,4-dimethoxybenzylidene)-1-cyclohexanone on aggregation and neurotoxicity of hen egg white lysozyme (HEWL) and, also, on spatial learning and memory of rats were evaluated.
30 male wistar rates (250-280 g) were divided into 5 groups: control, received scopolamine, received lysozyme amyloid aggregates, received lysozyme aggregates formed in presence of Curcumin and/or Curcumin derivative. The Morris Water maze was used for studying the spatial learning memory.
The results showed that, in comparison with receiver groups of lysozyme aggregates alone, the receiver rats of the aggregates formed in the presence curcumin and its derivative found platform in less time and with less distance traveled. The hippocampal injection of HEWL aggregates damaged the spatial memory of rates. Meanwhile amyloid aggregates formed in presence of curcumin or curcumin derivative were nontoxic and had no significant effect on spatial memory in rats.
These observations suggest that Curcumin and its derivativeare are capable to insert directly into amyloidogenic core of early aggregates and inhibiting amyloid fibril formation. Also, this study showed the importance of using model proteins as a valid tool to investigate the pathogenesis of Alzheimer’s disease.