Scientists at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), an autonomous institute of the Department of Science and Technology (DST), in Bangalore have discovered that abundant naturally occurring plant-based polyphenols (PPs) like tannic acid found in twigs of trees like chestnut and oak can modulate the ferroptosis-AD axis to yield a cost-effective strategy for the treatment of Alzheimer’s disease (AD) and help reduce the societal burden of this neurodegenerative disorder.
As per the Ministry of Science & Technology, Ferroptosis, an iron-dependent form of programmed cell death, has emerged as a significant contributor to the development of Alzheimer’s . Several hallmarks of Alzheimer’s, such as abnormal iron build up, lipid peroxidation, reactive oxygen species (ROS), and reduced activity of the antioxidant enzyme glutathione peroxidase 4 (GPX4), align with the defining characteristics of ferroptosis.
GPX4, the master regulator of ferroptosis reduces toxic lipid peroxides formed by the iron-catalysed reaction of polyunsaturated fatty acids (PUFAs) with ROS to lipid alcohol and acts as a first line of defence against ferroptosis. This is called the GPX4 pathway. However, the focus till now has been on chelating iron and neutralizing ROS, the potential therapeutic strategies that target GPX4 pathway to alleviate ferroptosis in Alzheimer’s have remained unexplored.
Polyphenol-based approach to treat Alzheimer’s
The research presents naturally occurring polyphenols (PPs) as innovative and multimodal therapeutic agent with dual capabilities to ameliorate ferroptosis and Alzheimer’s. The underlying mechanisms involve the inhibition of aggregation of amyloid (abnormal fibrous, proteinaceous deposits found in organs and tissues) and tau protein (abundantly found in the neurons of the central nervous system), diminishing oxidative stress and inhibiting ferroptosis. Their study has demonstrated that the natural polyphenol, Tannic Acid (TA) , could be both activator and enhancer of GPX4. This novel approach provides an advanced and comprehensive strategy for combating Alzheimer’s by modulating the GPX4-ferroptosis-AD axis. The ability of TA to elevate GPX4 levels even in the presence of AD pathological conditions offers new avenues for targeting novel pathways in the aetiology of Alzheimer’s while holding promise for tackling the intricate interplay between ferroptosis and Alzheimer’s.
This discovery may inspire medicinal chemists to explore new and derivatives of natural compounds to enhance therapeutic efficacy against Alzheimer’s.
With a potential to target both Alzheimer’s and ferroptosis simultaneously, tannic acid has been identified as a multifunctional molecule, establishing itself as a potent candidate for mitigating several pathways of Alzheimer’s and ferroptosis.
