Investigating Neuroprotective Effect of TLR4 Inhibitors in Alzheimer's Disease

Abstract

Objectives and Background: Alzheimer’s disease is a neurodegenerative disorder causing dementia by accumulation of amyloid β plaques and tau tangle in brain. The AlCl3 administration in rats induces Alzheimer’s disease successfully, which can be observed by behavioral parameters in rats. Toll like receptors 4 are involved in triggering the immune and inflammation reactions. Blocking of TLR4 might provide better target for future treatment of Alzheimer’s. Taxifolin is found to be anti inflammatory. The study is focused on the observation on the neuroprotective effects of Taxifolin against the AlCl3 induced AD models of rats. Experimental Procedure: Healthy, adult male rats are utilized for this experiment. Animals are divided into four groups; 1) Control group in which only saline as vehicle was administered, 2) Disease induced group, in which 25 mg/kg, i.p. AlCl3 was given to induce AD, 3) Treatment group (1 mg/kg, i.p.), in which after one week of AD induction AlCl3 + Taxifolin (1mg/kg) was given for another one week, 4) Treatment group (2mg/kg), in which after one week of AD induction and AlCl3 + Taxifolin (2 mg/kg, i.p.) was given for another one week. The present study, in addition to the estimation of oxidants (LPO, NO) anti-inflammatory (MPO) parameters were also evaluated for the memory impairment using pole test, Y- maze, and Morris water maze test and TLR4 expression in the brain tissue of rats using ELISA. Results: AlCl3 administration in rats resulted in memory loss, oxidative stress (increased lipid peroxide and nitric oxide), and augmentation of inflammation (MPO). It also resulted in the over expression of the TLR4 receptors in the brain tissues. Administration of taxifolin ameliorated the neurochemical, and behavioral consequences of chronic administration of AlCl3 in the rat. Conclusion: This experimental study clearly indicates that taxifolin acts as neuroprotective against the AD affected nerves by inhibiting TLR4 receptor. Taxifolin could be a potential treatment for Alzheimer’s disease protecting nerves from neuroinflammation and other complications.