Using chemical biology for neurodegenerative therapeutics
Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) are progressive neurodegenerative diseases characterized by a buildup of proteins or inflammation in the brain. The ALS disease pathology has been linked to an amino nuclear protein, TDP-43, which has functions related to the survival of motor neurons. AD pathology has been linked to neurofibrillary tangles caused by accumulation of the Tau protein, the buildup of beta-amyloid plaques, and chronic inflammation. The goal was to target the mutations in TDP-43 protein aggregation in ALS and the protein-protein interaction between CD44 and the FERM domain protein Moesin in AD for therapeutics treatment for the pathology of these diseases. Therapeutics were found using in-silico docking, and two compounds were used as therapeutics for ALS and AD: rTRD01 and P1 respectively. A Drosophila model was used for in-vivo experiments. Both biochemical assays (western blots and protein quantification) and behavioral assays (climbing assays) were performed to gage the effect of the therapeutic. The results demonstrated the therapeutics lowering the levels of the targeted protein when administered earlier in the pathology of the disease.
