Multipronged strategies to develop diagnostic and therapeutic agents for Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common form of demnetia. There are no approved diagnosis or disease modifying therapies for AD. Current treatments are only symptomatic and temporary, do not directly target the mechanisms underlying the disease processes. The production, accumulation and aggregation of amyloid beta (Aβ) peptide in the human brain is considered as one of the hallmarks of the disease. Moreover, Aβ in presence of redox-active metal ions responsible for additional trait of cellular toxicity induced by the generation of excessive chemically reactive species leading to oxidative stress, inflammation and aberrant neuronal activity, all of which leads to multifaceted toxicity in AD. Oxidative stress and anti-inflammatory responses contribute significantly towards the disease pathogenesis. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the major sources of oxidative stress in cells, which damage proteins, lipids, and DNA. The sequestartion of metal such as copper, iron and prevention of redox process, ROS generation and resultant oxidative stress and inflammatory response have huge implications in the treatment of AD. In this context, we have adopted multipronged strategies to develop diagnostic and therapeutic agents to modulate multifaceted toxicity. I shall present our recent results on the development of multifunctional modulators of Aβ toxicity and diagnostic probes. Furthermore, the nontoxic nature, prvention of ROS/RNS generation, and good antioxidant and anti-inflammatory effects of the lead candidates holds the key for developing therapeutics to alleviate multifaceted toxicity in AD.




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