Development of curcumin based probe for tau and amyloid imaging

• Main Author: Satnam Singh
• Other Authors: Manojit Pramanik
• Format: Theses and Dissertations
• Language: English
• Published: 2018
• Subjects: DRNTU::Engineering::Bioengineering
• Online Access: http://hdl.handle.net/10356/75261
• Institution: Nanyang Technological University

Recently, there has been rising attention in the fluorescence imaging probes of tau fibrils and amyloid beta for the early detection of Alzheimer’s disease (AD). One of the predominant causes of Alzheimer’s disease (AD), is the accumulation of hyper-phosphorylated tau protein forming neurofibrillary tangles (NFTs) and accumulation of amyloid beta aggregates which degenerate the neurons. Current research focuses on developing probes to target these aggregates with the help of molecular imaging techniques such as PET, MRI, Optical imaging etc. Despite knowing the pathological phenotypes of the disease and approach on development of fluorescent probes very well, there hasn’t been developed a single test which can diagnose the disease appropriately. Considering the necessity for AD diagnosis, we have synthesized 6 curcumin based fluorescent compounds to screen against tau fibrils and amyloid beta. Curcumin known for its anti-oxidant and anti-inflammatory effect, has also taken a role as a fluorescent probe for detecting tau fibrils and amyloid plaque. Our research also focuses on the development of the in-vitro cell model to test these curcumin derivatives. Hence, we have also aimed to develop in-vitro cell and brain tissue model based on the following two platforms to target the tau and amyloid plaques of AD. i) Transfection of EGFP-Tau-383 (0N4R) isoform into SHSY-5Y cells and showing a co-localization of EGFP with a fluorescent probe of interest, ii) Another platform includes sectioning the brain of a triple transgenic mouse and comparing the tau and amyloid beta targeting ability of fluorescent probe. In this research, we are using reference stains of Thioflavin S and Thioflavin T for standardization purposes. We are aiming to synthesize curcumin derivatives, which will overcome the blood brain barrier and the neuronal cell-membrane permeability factor and allow us to image tau fibrils and amyloid beta plaques, using the in-vitro cell models that we have developed.