Thangarajan Sumathi
University of Madras, India
Title: Neuroprotective insights of isorhamnetin against amyloid β(25-35)-induced oxidative insult and neuronal degeneration in rodent model: Perspectives on future therapeutics for Alzheimer's disease
Biography
Biography: Thangarajan Sumathi
Abstract
The amyloid-β (Aβ) is the major protein component of brain senile plaques in Alzheimer’s disease (AD) and is known to be directly responsible for the production of free radicals toxic to brain tissue. The present study was designed to elucidate the neuroprotective effect of Isorhamnetin (IRN), a flavone aglycones against the pathogenesis of AD. Experimental AD in rats was produced by intracerebroventricular administration of Aβ (25-35) peptide. Employing the following strategies of neurobehavioral, biochemical, immunohistochemistry, docking and molecular approach, we explored the attenuating effects of IRN against Aβ (25-35) peptide induced hippocampal neuronal loss and memory impairment. The present study has proven that IRN also reduced the expression of BACE-1 via inactivation of GSK3β and NFκB inhibition thereby inhibiting the accumulation of Aβ. Furthermore, IRN up regulated the phosphorylated GSK-3β and down regulated the expression of phosphorylated P-38 thereby inhibiting the Nrf-2 ubiquitination and improved the nuclear translocation of Nrf-2 which subsequently alleviated the expression of inflammatory cytokines which further reduced the ROS and RNS generation. Considering all the results, it can be suggested that IRN not only acts via antioxidant and anti-inflammatory activity but also by modulating the expression and function of AD related proteins. Hence, an amalgamation of in vivo, in vitro and in silico evidence might be supportive to delineate the neuroprotective potentials of IRN in the therapy of AD.