Research

Life Sciences & Biotechnology

Title :

Molecular and cellular mechanisms underlying the Lead exposure and cognitive impairment in Alzheimers disease and pharmacological intervention with Fraxetine

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Alavala sateesh, National Institute Of Nutrition, Telangana, Hyderabad

Timeline Start Year :

2024

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with a rising frequency driven by life expectancy. Around 45 million cases are recognized, with projection studies predicting a tripling of this number by 2050. Factors such as genetic mutations, lifestyle, and environmental pollutants contribute to AD. Lead (Pb) is a multifaceted pollutant with pathophysiological effects, including cognitive decline and neurological problems. Pb poisoning has been linked to AD in recent studies due to its capacity to target pathways implicated in AD pathogenesis. Research suggests that mitochondrial dysfunction is a pathogenic feature of AD, and Pb causes mitochondrial oxidative stress by decreasing complex III activity in the electron transport chain, increasing reactive oxygen species production, and decreasing the antioxidant defense mechanism of the cell. In vivo and in vitro studies demonstrate that Pb exposure has a causal effect on AD-linked characteristics such as Aβ aggregation and tau phosphorylation. Pb effects arise selectively after early-life exposure, implying an epigenetic mechanism. Fraxetin, a simple coumarin found in medicinal plants, has health-promoting qualities like anti-inflammatory, neuroprotective, antioxidant, and protective against ischemic stroke. This study investigates the underlying mechanism in both in vitro and in vivo models.

Organizations involved