Attenuation of dementia by AS605240‐PI3K inhibitor in ICV‐STZ induced sporadic Alzheimer's disease rat model

Abstract

Sporadic Alzheimer's disease is an age allied neurological and psychiatric disorder branded by impaired energy metabolism. Oxidative stress and neuro‐inflammation are associated in pathophysiology of sporadic type of dementia. The quest for chemical entities able to kerb the action of the PI3K/AKT/mTOR pathway is evolving as a potential therapeutic stratagem for its treatment and/or prevention.The Intra‐cerebroventricular (ICV) administration of streptozotocin prompts behavioural and biochemical changes resembling those in sporadic type of Alzheimer's patients. The current study was intended to investigate the effects of chronic pre‐treatment with Phosphoinositide 3‐kinase(PI3K)inhibitor AS605240 on cognitive dysfunction and oxidative stress markers in intracerebroventricular (ICV) streptozotocin‐treated albino rats.Treatment with AS605240 orally was done on a daily basis for a period of 21 days, 1 hr prior to ICV‐STZ injection using stereotaxy and evaluated for cognitive function tests and biochemical parameters.AS605240 when given orally on a daily basis for a period of 21 days significantly improved STZ‐induced cognitive impairment. Besides, improving cognitive dysfunction, AS605240, reduced elevated nitrite levels, and restored reduced glutathione and superoxide dismutase levels, Lipid peroxidation and total Protein content.Taken together, these results demonstrate that PI3K inhibitor AS605240 can be helpful in treatment of sporadic Alzheimer's Disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.