RETRACTED: Therapeutic prospects of modulating TLR4/MAPK/ROS signalling in obesity-associated neuroinflammation
Drashti Sharma, Ram Narayanan Ravi, Amar Daud Iskandar Abdullah, Vetriselvan Subramaniyan
Abstract
It is becoming more widely acknowledged that obesity is a chronic low-grade inflammatory disease that has a significant influence on brain health in addition to metabolic problems. Adipose tissue growth, macrophage polarization, and cytokine release all contribute to systemic inflammation, which weakens the blood-brain barrier (BBB) and promotes immune-to-brain communication. Saturated fatty acids and gut-derived lipopolysaccharides activate Toll-like receptor 4 (TLR4) in the central nervous system, which triggers downstream nuclear factor-κB (NF-κB) and Mitogen-activated protein kinase (MAPK) cascades and increases neuroinflammation. At the same time, mitochondrial malfunction and oxidative stress hasten the buildup of reactive oxygen species (ROS), which further primes the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and maintains glial hyperactivation. These processes work together to cause synaptic dysfunction, insulin resistance in neurons, and heightened susceptibility to neurodegenerative illnesses, including Parkinson's and Alzheimer's. Pharmacological inhibitors, natural substances, and lifestyle changes that target TLR4, MAPK signaling, and ROS-mediated pathways have the potential to disrupt this metabolic-inflammatory-neuronal axis. Developing comprehensive solutions to reduce obesity-driven neuroinflammation requires an understanding of the molecular interactions between peripheral metabolic stress and central immune activation. • Obesity acts as a chronic low-grade inflammatory disease affecting brain health. • Adipose inflammation and cytokines disrupt BBB integrity and activate glial cells. • TLR4/MAPK/ROS–NLRP3 signalling drives obesity-linked neuroinflammation. • Targeting TLR4, MAPK, and mitochondrial ROS offers therapeutic potential. • Combined lifestyle and pharmacological strategies provide optimal protection.