Research Projects

Alzheimer's disease (AD) and other dementia forms are a growing public health issue, with approximately 50 million people suffering from dementia worldwide. south Asia, particularly India, is a major contributor to this number, with sporadic AD (sAD) accounting for 90% of AD cases. The pathogenesis of sAD is poorly understood, and no effective therapeutics have been developed so far. Metabolic dysfunctions like diabetes have been suggested to be associated with sAD, leading to the name "brain diabetes" or Type 3 Diabetes (T3D). Dysregulated blood glucose increases the risk of developing AD, and insulin resistance contributes to the pathogenesis of sAD through multiple pathways. Desensitization of insulin receptors on neurons leads to reduced glucose utilization, decreased ATP production, altered energy metabolism, and neuronal cell death. Altered insulin signalling, cholesterol, and glucose homeostasis may induce neuronal dysfunctions, cell death, and cognitive impairment. Liver X receptors (LXRs) are transcription factors that regulate cholesterol and lipid, glucose metabolism, inflammation, amyloidogenesis, and neurogenesis. In an insulin-resistant state, cells fail to utilize glucose, leading to impaired LXR signaling and defective neurogenesis and loss of synaptic plasticity. The present study aims to investigate the role of LXR in glucose, cholesterol homeostasis, and downstream processes such as neurogenesis, inflammation, and lipid rafts organization. The study will assess the status of LXR and its targets genes, cholesterol and glucose homeostasis, inflammatory markers, lipid rafts organization, and amyloidogenesis using biochemical, molecular, and histological methods. The findings are expected to identify specific molecular targets for the treatment and prevention of sAD.