Research Projects

The current diagnosis of Alzheimer's Disease (AD) is primarily based on assessing the cognitive state of patients, which is already in an advanced stage. The development of novel theranostic agents that can diagnose and treat at an early stage provides a realistic opportunity to control underlying pathologies associated with the disease. Acetyl and butyryl cholinesterases (AChE and BChE) are strongly associated with memory impairment and other cognitive functions in AD. Existing radiotracer diagnostic tools, such as PET imaging for AChE/BChE, are expensive and have limited availability for primary patient screening and preclinical animal studies. Small molecular near-infrared fluorescent (NIRF) probes may serve as an inexpensive, handy theranostic tool to comprehend the dynamics of pathogenic progression in AD. The proposed project aims to synthesize novel smart theranostic agents to develop a meaningful SAR of the designed novel series of molecules and carry out mechanistic studies of the lead probes. The selection of probes (2-3 from each series) for detailed biological evaluation is based on in-vitro assays. To mimic the early and late stages of the disease, the inhibitory potency against AChE/BuChE of the developed TPs will be carried out with different concentrations of the enzymes at different time points. The age-dependent change in the level of AChE/BChE in mice will be examined before testing the probes in the AD mice model. In the tissue-specific transgenic Drosophila Alzheimer's model, the AChE/BChE expression levels during brain development will be detected.